Publisher: Elsevier   (Total: 3206 journals)

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Showing 1 - 200 of 3206 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 39, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 27, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 106, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 44, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 8)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6)
Acta Astronautica     Hybrid Journal   (Followers: 450, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 30, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 3)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 11, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 5, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 338, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 3, SJR: 1.793, CiteScore: 6)
Acta Psychologica     Hybrid Journal   (Followers: 26, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access   (Followers: 1)
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 7, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 8)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 18, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 9, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 14, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 195, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 13, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 20, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 30, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 12, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 12, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 15, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 35, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 5)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 29, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 11, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 11, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 27, SJR: 1.562, CiteScore: 3)
Advances in Clinical Radiology     Full-text available via subscription   (Followers: 1)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 21, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Cosmetic Surgery     Full-text available via subscription   (Followers: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 16)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 14)
Advances in Digestive Medicine     Open Access   (Followers: 14)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 26)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 30, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 9)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 51, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 2)
Advances in Family Practice Nursing     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 69, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 21, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 8, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 26, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 26)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 4, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 37, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 10, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 21, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 17, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 9, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 26)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Pathology     Hybrid Journal   (Followers: 1)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 5)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Ophthalmology and Optometry     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 18, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 6, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 27, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 19)
Advances in Pharmacology     Full-text available via subscription   (Followers: 17, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 10)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 6)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 69)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 3, SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 7)
Advances in Space Research     Full-text available via subscription   (Followers: 434, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 6)
Advances in Surgery     Full-text available via subscription   (Followers: 13, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 36, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 20)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 6, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 57, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 398, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 12, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 485, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 18, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 32, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 47, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 58, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 8, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 12)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 2, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 11, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 56, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 6, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 6, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 59, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 67, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 48, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 13)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 17, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 40, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 35, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 37, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 51)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics & Gynecology MFM     Hybrid Journal   (Followers: 1)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 276, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 67, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 32, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 29, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 39, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 67, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 26, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 6, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 44, SJR: 1.512, CiteScore: 5)
Analytica Chimica Acta : X     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 223, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 13, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 14)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 25, SJR: 0.683, CiteScore: 2)

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Similar Journals
Journal Cover
Journal Prestige (SJR): 1.153
Citation Impact (citeScore): 3
Number of Followers: 12  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0741-8329 - ISSN (Online) 1873-6823
Published by Elsevier Homepage  [3206 journals]
  • Risky Drinking Decisions: The Influence of Party Music and Alcohol Abuse
           in Young Adult Women
    • Abstract: Publication date: Available online 15 May 2019Source: AlcoholAuthor(s): Anastasia I. Nikoulina, Lindsay R. Arcurio, Peter R. Finn, Thomas W. JameAbstractMusic is a ubiquitous feature of young adults’ social drinking environments, yet no studies have assessed whether and how it impacts risky decisions to drink alcohol. Previous research on the influence of music on risky decisions is largely based around decision tasks with monetary incentives.MethodsTo assess the impact of music listening on risky drinking decisions, the current study used visual alcohol cues paired with hypothetical risky drinking scenarios (e.g. “You do not have a safe ride home,” for alcohol). Young adult women with a history of alcohol abuse (N = 34), and casual-drinking control women (N = 29), made hypothetical decisions about whether or not to drink alcohol, or eat food (an appetitive control condition), in risky contexts while personal “party music” (music chosen by participants for “going out”) and “home music” (music chosen for “staying in”) played in the background. The main dependent measure – likelihood of drinking – was reported on a 4-point scale where 1 corresponded to “very unlikely,” and 4 to “very likely.”ResultsListening to party music while making decisions increased the likelihood of making risky drinking decisions regardless of a history of alcohol abuse, while other personal music did not. Further, party music specifically increased the likelihood of risky drinking decisions relative to risky eating decisions. As expected, those with a history of alcohol abuse made more risky drinking decisions in general, regardless of the type of music heard.DiscussionThe results suggest that party music is an important feature of the drinking environment associated with increased risky decisions about drinking alcohol in young adult women, regardless of their history of alcohol abuse. The finding that music plays an important role in risky drinking decisions indicates that further investigation into the real-world drinking environments of young adults is crucial, as it will aid in the development of a more complete picture of risky drinking decisions in young adults.
  • Sexually divergent changes in select brain proteins and neurosteroid
           levels after a history of ethanol drinking and intermittent PTSD-like
           stress exposure in adult C57BL/6J mice
    • Abstract: Publication date: March 2020Source: Alcohol, Volume 83Author(s): Leslie L. Devaud, Mehrdad Alavi, Jeremiah P. Jensen, Melinda L. Helms, Michelle A. Nipper, Deborah A. FinnAbstractHuman studies reported that the number of past-year stressors was positively related to current drinking patterns, including binge drinking. In animal models, exposure to predator odor stress (PS), considered a model of traumatic stress, consistently increased ethanol intake. Recently, we reported that repeated PS significantly increased ethanol intake and had a synergistic interaction with prior binge drinking (binge group) in male but not in female C57BL/6J mice, when compared to mice without prior binge exposure (control group). The current studies utilized plasma and dissected prefrontal cortex (PFC) and hippocampal tissue from these animals and from age-matched naïve mice (naïve group). Western blots assessed relative protein levels of P450scc (an enzyme involved in the first step of steroidogenesis), of GABAA receptor α2 and α4 subunits, and of two proteins involved in synaptic plasticity – ARC (activity-regulated cytoskeletal protein) and synaptophysin. Gas chromatography-mass spectrometry simultaneously quantified 10 neurosteroid levels in plasma. A history of ethanol drinking and PS exposure produced brain regional and sex differences in the changes in proteins examined as well as in the pattern of neurosteroid levels versus (vs.) values in naïve mice. For instance, P450scc levels were significantly increased only in binge and control female PFC and hippocampus vs. naïve mice. Some neurosteroid levels were significantly altered by binge treatment in both males and females, whereas others were only significantly altered in males. These sexually divergent changes in neurosteroid and protein levels add to evidence for sex differences in the neurochemical systems influenced by traumatic stress and a history of ethanol drinking.
  • Influence of moderate beer consumption on human gut microbiota and its
           impact on fasting glucose and β-cell function
    • Abstract: Publication date: Available online 12 June 2019Source: AlcoholAuthor(s): Fernando Hernández-Quiroz, Khemlal Nirmalkar, Loan Edel Villalobos-Flores, Selvasankar Murugesan, Yair Cruz-Narváez, Enrique Rico-Arzate, Carlos Hoyo-Vadillo, Alejandra Chavez-Carbajal, María Luisa Pizano-Zárate, Jaime García-MenaBeer is a beverage consumed worldwide for thousands of years due to social, religious, and cultural reasons, it contains polyphenolic compounds as well as phenolic acids with a potential positive effect in human health. This study aimed to explore the impact of moderate beer consumption in human health and gut microbiota function. 355 mL of non-alcoholic beer (NAB) or alcoholic beer (AB) were consumed daily by the participants for 30 days in each study. Anthropometric measures, blood samples for biochemistry, and fecal samples for microbiota analysis were collected on day 1 and 30. Microbial diversity was characterized by high throughput sequencing of 16S rDNA libraries, and data were analyzed using QIIME pipeline. We found, NAB and AB, have effect on the composition of the gut microbiota favoring the proliferation of Bacteroidetes with respect to Firmicutes. No increase in weight, waist, and hip parameters was observed, and the liver and lipid profile values were not modified only for NAB. In addition, the consumption of NAB induced a decrease in fasting blood serum glucose and an increase in functional β cells, while, on the other hand, there was an increase in blood serum glucose and decreased in functional β cells with the consumption of AB. In general, beer consumption neither change anthropometric values, nor affected liver function and although the glucose values decreased with NAB or increased with AB, they remained within normal range. Our conclusion is that moderate consumption of NAB has a positive effect on human health by supplementation of biological active polyphenol and phenolic acids, and by enrichment of the gut microbiota diversity with beneficial bacteria; while the presence of alcohol in AB interferes with this effect in our study. More work should be made on this topic before more general conclusions are drawn.Graphical abstractGraphical abstract for this article
  • MUNC13-1 heterozygosity does not alter voluntary ethanol consumption or
           sensitivity in mice
    • Abstract: Publication date: March 2020Source: Alcohol, Volume 83Author(s): Jessica I. Wooden, Kyle Schuller, Gregg Roman, Joydip Das, J. Leigh LeasureAbstractThe role of the munc13–1 presynaptic protein in alcohol-related behaviors has been little-studied, despite being a known site of action for ethanol binding. Munc13–1 is an active zone protein that plays a vital role in vesicle maturation and the release of neurotransmitters in excitatory neurons. Ethanol binds munc13–1, which decreases its functionality. In Drosophila, loss of the homologous protein Dunc13 is associated with an increase in ethanol preference, and is associated with a resistance to sedation following ethanol exposure. The current study assessed the effects of munc13-1 heterozygosity on ethanol sensitivity and consumption in mice, as well as on learning and anxiety-like behaviors, which can influence alcohol intake. Wild-type and mutant mice underwent 6 cycles of drinking-in-the-dark (DID) as well as rotarod testing following ethanol injection, to probe for differences in ethanol consumption and sensitivity, respectively. We did not detect genotype-based differences in our measures of anxiety, spatial learning, ethanol consumption, or ethanol sensitivity. However, heterozygotes showed increased use of a spatial navigation strategy in a dual-solution water maze, as opposed to a stimulus-response strategy. To summarize, although reduction of Dunc13 in flies produces clear effects on ethanol consumption and sensitivity, heterozygosity for munc13-1 does not, potentially due to compensatory adaptation by other munc-13 isoforms.
  • Chronic alcohol-induced liver injury correlates with memory deficits: Role
           for neuroinflammation
    • Abstract: Publication date: March 2020Source: Alcohol, Volume 83Author(s): Jean A. King, Benjamin C. Nephew, Asmita Choudhury, Guillaume L. Poirier, Arlene Lim, Pranoti MandrekarAbstractAlcohol use disorder (AUD) affects over 15 million adults over age 18 in the United States, with estimated costs of 220 billion dollars annually – mainly due to poor quality of life and lost productivity, which in turn is intricately linked to cognitive dysfunction. AUD-induced neuroinflammation in the brain, notably the hippocampus, is likely to contribute to cognitive impairments. The neuroinflammatory mechanisms mediating the impact of chronic alcohol on the central nervous system, specifically cognition, require further study. We hypothesized that chronic alcohol consumption impairs memory and increases the inflammatory cytokines TNFα, IL6, MCP1, and IL1β in the hippocampus and prefrontal cortex regions in the brain. Using the chronic-binge Gao-NIAAA alcohol mouse model of liver disease, representative of the drinking pattern common to human alcoholics, we investigated behavioral and neuroinflammatory parameters. Our data show that chronic alcohol intake elevated peripheral and brain alcohol levels, induced serum alanine aminotransferase (ALT, a marker of liver injury), impaired memory and sensorimotor coordination, and increased inflammatory gene expression in the hippocampus and prefrontal cortex. Interestingly, serum ALT and hippocampal IL6 correlated with memory impairment, suggesting an intrinsic relationship between neuroinflammation, cognitive decline, and liver disease. Overall, our results point to a likely liver-brain functional partnership and suggest that future strategies to alleviate hepatic and/or neuroinflammatory impacts of chronic AUD may result in improved cognitive outcomes.
  • Alcohol Use Disorders Identification Test (AUDIT): Validation of the
           Persian Version in an Iranian Population
    • Abstract: Publication date: Available online 15 August 2019Source: AlcoholAuthor(s): Hosein Rafiemanesh, Kamran Yazdani, Saharnaz Nedjat, Alireza Noroozi, John B. Saunders, Ramin Mojtabai, Afarin Rahimi-MovagharAbstractBackground and AimsIt is important to incorporate a screening test for unhealthy alcohol use into primary and other health care settings. The Alcohol Use Disorders Identification Test (AUDIT) is one of the most commonly used of such tests. The objectives of this study were to evaluate the psychometric properties of the Persian version of AUDIT, and to determine the best cut-off points for detection of hazardous drinking and alcohol use disorders.MethodsWe translated the AUDIT to Persian and assessed its face and content validity, reliability and criterion validity against the diagnosis of alcohol use disorders according to the International Classification of Diseases, 10th Revision (ICD-10) diagnostic guidelines, as assessed using the Composite International Diagnostic Interview (CIDI). We determined the best cut-off points for detection of hazardous use, harmful use, and dependence using receiver operating characteristic (ROC) curve analysis. Psychometric properties were assessed in a sample of 400 participants attending medium-term residential drug treatment centers located in Tehran, Iran.ResultsThe Persian AUDIT had high internal consistency (Cronbach’s alpha = 0.88), and test-retest reliability (intraclass correlation coefficient = 0.84). The questionnaire also had excellent face and content validity as well as criterion validity when compared with CIDI. The best cut-off points for alcohol dependence, harmful use, and hazardous use were 11 (sensitivity = 95.6, specificity = 80.4), 7 (sensitivity = 85.5, specificity = 84.2), and 5 (sensitivity = 87.6, specificity = 92.9), respectively.ConclusionsThe Persian version of the AUDIT has excellent psychometric properties as a screening tool for alcohol use disorders and hazardous alcohol use in settings in which alcohol use is common. Further research on the AUDIT in the general population and in primary health care settings is warranted.
  • Inverse association between habitual alcohol drinking and d-dimer in
           patients with type 2 diabetes mellitus
    • Abstract: Publication date: Available online 11 July 2019Source: AlcoholAuthor(s): Mikio Marumo, Kazumi Ekawa, Shigeyuki Ebara, Ichiro WakabayashiAbstractAlcohol is known to inhibit blood coagulation. Patients with diabetes mellitus are prone to show hypercoagulability. However, it remains to be clarified whether and how habitual alcohol drinking affects coagulability in patients with diabetes. The purpose of this study was to determine the relationship between alcohol intake and d-dimer, a sensitive marker of blood coagulation, in patients with diabetes. We investigated the relationship between alcohol intake and d-dimer in plasma of 269 patients with type 2 diabetes by using analysis of covariance and logistic regression analysis after adjustment for age, gender, body mass index, hemoglobin A1c, and histories of smoking and anti-coagulation therapy. Log-transformed d-dimer and HDL cholesterol were significantly lower and higher, respectively, in regular drinkers than in nondrinkers, while there were no significant differences in log-transformed d-dimer and HDL cholesterol in occasional drinkers and nondrinkers. Odds ratios of regular drinkers vs. nondrinkers for high d-dimer (0.46 [0.21-0.98]) and low HDL cholesterol (0.20 [0.08-0.50]) were significantly lower than the reference level, while the odds ratios of occasional drinkers for high d-dimer (1.24 [0.41-3.73] and low HDL cholesterol (0.43 [0.15-1.25]) were not significantly different from the reference level. HDL cholesterol showed a significant inverse correlation with log-transformed d-dimer both in overall subjects and in nondrinkers. Regular drinking, but not occasional drinking, was associated with lower d-dimer levels, suggesting that habitual alcohol drinking suppresses hypercoagulability in patients with diabetes. There is an alcohol intake-independent inverse association between HDL cholesterol and d-dimer.
  • Alcohol-induced lipid dysregulation impairs glycolytic responses to LPS in
           alveolar macrophages
    • Abstract: Publication date: March 2020Source: Alcohol, Volume 83Author(s): William S. Slovinsky, Hoora Shaghaghi, Rachel Para, Freddy Romero, Ross SummerAbstractSeveral conditions are marked by increased susceptibility to, and enhanced severity of, bacterial infections. Alcohol use disorder, one of these conditions, is known to predispose to bacterial pneumonia by suppressing the lung's innate immune system, and more specifically by disrupting critical alveolar macrophage (AM) functions. Recently, we established that chronic ethanol consumption also perturbs surfactant lipid homeostasis in the lung and that elevated concentrations of free fatty acids contribute to blocking essential AM functions, such as agonist-induced cytokine expression. In this study, we extend these observations by showing that elevated free fatty acid levels impair metabolic responses to lipopolysaccharide (LPS) in AMs. In particular, we show that the glycolytic reprogramming characteristic of LPS-stimulated AMs is blunted by the saturated fatty acid palmitate, whereas oleate, an unsaturated fatty acid, or ethanol alone, had no effect on this adaptive metabolic response. Additionally, we found that elevated concentrations of palmitate induced mitochondrial oxidative stress and that glycolytic reprogramming and cytokine production to LPS could be partially restored in AMs by either pharmacologically blocking palmitate entry into mitochondria or administering a mitochondrial-specific antioxidant. Taken together, these findings suggest that alcohol and elevated levels of saturated fatty acids conspire to impair pulmonary innate immunity by altering metabolic responses in AMs. Additionally, our findings suggest that targeting the mechanisms involved in fatty acid metabolism can restore pulmonary immunity and possibly limit bacterial pneumonia in individuals with alcohol use disorder.
  • Overexpression of MHCII by hepatocytes in Alcoholic Hepatitis (AH)
           compared to Non-alcoholic Steatohepatitis (NASH) and normal controls
    • Abstract: Publication date: Available online 5 September 2019Source: AlcoholAuthor(s): Jiajie G. Lu, Askalu Iyasu, Barbara French, Brittany Tillman, Samuel W. French, Samuel W. French, M.DAbstractPreviously we have shown that in autoimmune hepatitis CD4 positive lymphocytes form an immunologic synapse with hepatocytes, leading to gradual diminishing and elimination of the hepatocyte. We wondered whether a similar mechanism may occur in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH). We conducted immunofluorescence studies of expression of MHCII, the binding partner of CD4, on patient liver biopsies of AH, NASH, and normal controls. In cases of alcoholic hepatitis, there was prominent sinusoidal expression of MHC II; In NASH biopsies there was comparatively lower expression of MHC II, but still more than control tissue. Immunohistochemical stain for CD4 showed CD4 positive lymphocytes closely associated with hepatocytes in AH biopsies. Furthermore, expression levels of the multifunctional cytokine IL-1α was higher in AH compared to NASH and control biopsies. These results underlie the more severe nature of alcoholic hepatitis and underscore the autoimmune mechanisms involved in the liver damage found in alcoholic hepatitis.
  • Suppression of voluntary ethanol intake in mice under constant light and
           constant darkness
    • Abstract: Publication date: March 2020Source: Alcohol, Volume 83Author(s): Alan M. Rosenwasser, Walter D. McCulley, Matthew C. Hartmann, Michael C. Fixaris, John C. CrabbeAbstractSeasonal variations in photoperiod are associated with alterations in human mood and behavior. Similarly, manipulation of the environmental lighting regimen can exert pronounced effects on affective behavior in experimental animals. These observations may be due, in part, to light-induced alterations in circadian rhythms, but it seems likely that other, non-circadian factors also contribute. Several studies have shown that voluntary alcohol (ethanol) consumption can be affected by lighting conditions in rodents, suggesting that photoperiodic variation may account for seasonal and geographic patterns of human alcohol consumption. Nevertheless, the existing animal data are somewhat inconsistent, and little work in this area has been performed in mice. In the present study, we monitored circadian activity rhythms and voluntary ethanol consumption under standard 12:12 light–dark (LD) cycles, and in constant light (LL) and constant darkness (DD). Experiment 1 employed male C3H/He inbred mice, while Experiment 2 employed males and females from a genetically heterogeneous line (WSC). Relative to LD conditions, ethanol intake and ethanol preference were reduced under both LL and DD in both experiments. Because similar effects were seen in both LL and DD, neither circadian disruption nor a classical photoperiodic mechanism are likely to account fully for these findings. Instead, we suggest that the absence of circadian entrainment may function as a mild stressor, resulting in reduced ethanol consumption.
  • Effects of pair-housing on voluntary alcohol intake in male and female
           Wistar rats
    • Abstract: Publication date: Available online 21 January 2020Source: AlcoholAuthor(s): Hayden Scott, Nikita Tjernström, Erika RomanA number of different voluntary alcohol intake paradigms are available for home cage drinking studies. Traditionally these paradigms involve single housing in order for individual intake to be measured. This study aimed at investigating the effects of pair-housing on voluntary alcohol intake. Male and female Wistar rats were housed in pairs or individually for studies of voluntary alcohol intake using the modified intermittent access paradigm with alcohol access during three consecutive days per week followed by four days of water only. Individual intake of 20% alcohol solution and water was measured during 12 sessions, i.e. 4 weeks. Pair-housed animals could interact freely with their cage mate for four consecutive days each week and were then separated by an inserted mesh divider for three consecutive days each week during alcohol intake sessions. Alcohol intake and preference was compared between pair- and individually housed rats. The results revealed higher alcohol intake in females than in males. Pair-housed males had a higher alcohol intake and preference during the first three weeks compared to individually housed males that thereafter ceased. No effect of housing condition was observed in female rats. The alcohol intake was higher on the first day of access relative to the two consecutive days in pair-housed males and higher on the first two days relative to the third in female rats. Social rank or female estrus cycle had no effect on alcohol intake or preference. Taken together, the use of a divider during alcohol intake sessions had no impact on alcohol intake in female rats and may not exert long-term influences in male rats. Future studies are needed in order to elucidate if the use of a divider can constitute an experimental refinement as an alternative to individual housing in studies of voluntary alcohol intake using the limited and intermittent access paradigms.Graphical abstractGraphical abstract for this article
  • An LC-MS/MS method for comparing the stability of ethanol's non-oxidative
           metabolites in dried blood spots during 90 days
    • Abstract: Publication date: March 2020Source: Alcohol, Volume 83Author(s): Hao Wang, Yi Zhang, Xinyu Zhang, Jiaolun Li, Zebin Lin, Zhibin Huang, Jing Chang, Yunfeng Zhang, Jingru Wang, Chengqiang Zhang, Yulan RaoAbstractProblems of stability were found for biomarkers of alcohol consumption: ethyl glucuronide (EtG), ethyl sulfate (EtS), phosphatidylethanols (PEths), and fatty acid ethyl esters (FAEEs) in whole blood. The purpose of this study was to establish a method for the determination of these four kinds of ethanol's non-oxidative metabolites in dried blood spots (DBS) by liquid chromatography tandem mass spectrometry (LC-MS/MS), and to evaluate their stability. In this method, 50 μL of human blood was spotted onto a filter paper for DBS analysis. Samples were extracted by methanol, reconstituted by 2-propanol, and injected into the LC-MS/MS system. Limits of detection were among 0.5–50 ng/mL, and deviations in accuracy and precision were all lower than 15% at three quality control levels. The stability of the four kinds of ethanol non-oxidative metabolites in DBS was investigated during a 90-day range under three temperatures, −20 °C, 4 °C, and 25 °C. EtG and EtS showed a high level of stability in DBS in the 90-day range, regardless of the temperature. FAEEs were unstable after three days. PEths showed stability within 15 days in postmortem DBS and 60 days in antemortem DBS, respectively, at all temperatures.
  • Active immunization against serum alcohol dehydrogenase normalizes brain
           dopamine metabolism disturbed during chronic alcohol consumption
    • Abstract: Publication date: March 2020Source: Alcohol, Volume 83Author(s): Nikita A. Mitkin, Petr K. Anokhin, Maria V. Belopolskaya, Olga Y. Frolova, Ekaterina A. Kushnir, Maxim L. Lovat, Vsevolod V. PavshintsevAbstractChronic ethanol consumption in high doses is associated with constitutively elevated activity of the serum alcohol dehydrogenase I (ADH I) isoform, which demonstrates a high affinity not only for ethanol but also for a number of bioamine metabolites. Such excessive ADH activity is probably associated with disruptions in the metabolism of neurotransmitters (dopamine, serotonin, and norepinephrine) and subsequent long-term changes in the activity of their receptors. Ultimately, a stable depressive-like condition contributes to the development of patients’ craving for ethanol intake, frequent disruptions during therapy, and low efficacy of treatment.We applied active immunization against ADH to investigate its efficacy in the reduction of excessive serum ADH activity and regulation of ethanol consumption by chronically ethanol-fed Wistar rats (15% ethanol, 4 months, free-choice method), and we analyzed its ability to influence the levels of bioamines in the brain. Immunization (2 injections, 2-week intervals) was performed using a combination of recombinant horse ADH isozyme as an antigen and 2% aluminum hydroxide-based adjuvant.The efficacy of immunization was demonstrated by the production of high titers of ADH-specific antibodies, which was consistent with the significantly reduced ADH activity in the serum of chronically ethanol-fed rats. On the 26th day after the first vaccine injection, we registered significantly lower levels of alcohol consumption compared to ethanol-fed control animals, and the difference reached 16% on the 49th day of the experiment. These observations were accompanied by data that showed reduced levels of ethanol preference in immunized rats. Chronic alcohol drinking led to a decrease in dopamine and DOPAL (a direct dopamine metabolite and a high-affinity ADH substrate) levels in the striatum,while immunization neutralized this effect. Additionally, we observed that inhibition of serum ADH activity caused a decrease in peak dopamine levels during acute alcohol intake in chronically ethanol-fed rats during ethanol withdrawal that was associated with reduced tyrosine hydroxylase activity in the striatum.The obtained data suggest a significant contribution of ADH to the changes in neurotransmitter systems during chronic alcohol consumption and make available new prospects for developing innovative strategies for treatment of excessive alcohol intake.
  • Perceptions of alcohol use among injury patients and their family members
           in Tanzanian society
    • Abstract: Publication date: March 2020Source: Alcohol, Volume 83Author(s): Brian J. Meier, Deena El-Gabri, Kaitlyn Friedman, Mark Mvungi, Blandina T. Mmbaga, João Ricardo Nickenig Vissoci, Catherine A. StatonAbstractAlcohol is one of the leading causes of death and disability worldwide. Rates of alcohol abuse in Moshi, Tanzania, are about 2.5 times higher than the Tanzanian average. We sought to qualitatively assess the perceptions of alcohol use among injury patients in Moshi, including availability, consumption patterns, abuse, and treatments. Participants were Emergency Department injury patients, their families, and community advisory board members. Participants were included if they were ≥18 years of age, a patient or patient’s family member seeking care at the Kilimanjaro Christian Medical Center Emergency Department, Moshi, Tanzania, for an acute injury, clinically sober at the time of enrollment, medically stable, able to communicate in Swahili and consented to participate. Focus group discussions were audiotaped, transcribed, translated, and analyzed in parallel using an inductive thematic content analysis approach. Resultant themes were then reanalyzed to ensure internal homogeneity and external heterogeneity. Fourteen focus group discussions, with a total of 104 participants (40 patients, 50 family members, 14 community advisory board members), were conducted. Major themes resulting from the analysis included: 1) Early/repeated exposure; 2) Moderate use as a social norm with positive attributes; 3) Complications of abuse are widely stigmatized; and 4) Limited knowledge of availability of treatment. Our findings suggest that, among our unique injury population and their families, despite the normalization of alcohol-related behaviors, there is strong stigma toward complications stemming from excess alcohol use. Overall, resources for alcohol treatment and cessation, although broadly desired, are unknown to the injury population.
  • Regular versus episodic drinking in Swedish women: reporting of regular
           drinking may be less biased by social desirability
    • Abstract: Publication date: Available online 9 January 2020Source: AlcoholAuthor(s): Monica Hunsberger, Kirsten Mehlig, Cecilia Björkelund, Lauren LissnerAbstractAimTo describe the personality and social characteristics associated with regular and episodic alcohol consumption in a Swedish cohort of women.Methods406 women aged 38 and 50 who participated in the Population Study of Women in Gothenburg in 2004-05 with complete data on the key variables are included. Regular alcohol use was based on frequencies of alcoholic beverage consumption, reported to examining physicians. Regular drinking was defined as those consuming wine, beer or spirits at least twice weekly. Episodic drinking was defined as consumption of six drinks or more on a single occasion at least once during the last year. Personality traits were studied using the self-administered 57-item Eysenck Personality Inventory, which includes a ‘lie scale’ measuring the tendency towards social desirability, a ‘neuroticism scale’, and an ‘extraversion scale’. Logistic regression was used to estimate odds ratios (OR) for regular and episodic drinking, respectively, in relation to standardized (SD) personality scores and selected social characteristics.Results49% of the women reported episodic drinking, while 58% reported regular drinking and 34% reported both. Women with a higher tendency towards socially desirable responses were less likely to report episodic drinking (odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.53-0.84) per standard deviation (SD), a trait that was not associated with regular drinking.ConclusionsThe strong inverse association between the propensity to lie scale with episodic but not regular drinking suggests that episodic drinking is subject to greater social desirability and under-reporting biases than regular drinking. Our findings indicate that this type of problem drinking may be missed in medical examinations, which limits the ability of health professionals to intervene.
  • Association of change in alcohol consumption on fasting serum glucose,
           insulin resistance, and beta cell function among Korean men
    • Abstract: Publication date: Available online 9 January 2020Source: AlcoholAuthor(s): Seulggie Choi, Gyeongsil Lee, Jiyoung Kang, Sang Min Park, Eunju Sung, Ho-Cheol Shin, Cheol Hwan KimAbstractWe aimed to determine the association between alcohol consumption change on fasting serum glucose, insulin resistance, and beta cell function. The study population consisted of 55,858 men from the Kangbuk Samsung Health Study. Participants were divided into non-, light, moderate, and heavy drinkers for each of the first and second health examinations based on a self-reported questionnaire on alcohol consumption. The adjusted mean values for change in fasting serum glucose (FSG), homeostatic model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-β) levels were determined according to alcohol consumption change by linear regression. Compared to sustained initial drinkers, those who increased alcohol intake to moderate (p
  • Effects of pharmacological inhibition of the centrally-projecting
           Edinger-Westphal nucleus on ethanol-induced conditioned place preference
           and body temperature
    • Abstract: Publication date: Available online 9 January 2020Source: AlcoholAuthor(s): Alfredo Zuniga, Andrey E. Ryabinin, Christopher L. CunninghamAbstractAlcohol use disorder is a chronic disease characterized in part by repeated relapsing events. Exposure to environmental stimuli or cues that have previously been associated with the effects of alcohol can promote relapse through the triggering of craving for alcohol. Therefore, identifying and characterizing neuronal populations that may regulate these associations is of the upmost importance. Previous studies have implicated the centrally-projecting Edinger Westphal nucleus (EWcp) in this process, as the EWcp is both sensitive to, and can regulate alcohol intake. To date however, it is unclear if the EWcp is involved in the formation or expression of these alcohol-cue associations. As such, the present studies examined the involvement of the EWcp in male DBA/2J mice in the acquisition and expression of place preference for an alcohol-paired cue using the conditioned place preference (CPP) procedure. Pharmacological inhibition of the EWcp via the GABAA and GABAB receptor agonists muscimol and baclofen did not affect either the acquisition or the expression of CPP. Follow up studies did find however, that pharmacological inhibition of the EWcp increased body temperature and prevented alcohol-induced increases in c-Fos expression in the EWcp. When considered in light of previous studies, the present results indicate that the EWcp may be involved in the regulation of alcohol self-administration, and not conditioned alcohol-seeking. Additionally, the present studies provide further evidence for the involvement of the EWcp in thermoregulation and help elucidate the molecular mechanism by which alcohol increases c-Fos in the EWcp.
  • Cigarette Smoking History is associated with Poorer Recovery in Multiple
           Neurocognitive Domains Following Treatment for an Alcohol Use Disorder
    • Abstract: Publication date: Available online 7 January 2020Source: AlcoholAuthor(s): Timothy C. Durazzo, Dieter J. MeyerhoffAbstractCigarette smoking is associated with neurocognitive dysfunction in various populations, including those seeking treatment for an alcohol use disorder (AUD). This study compared the rate and extent of recovery on measures of processing speed, executive functions, general intelligence, visuospatial skills and working memory in treatment-seeking alcohol dependent individuals (ALC) who were never-smokers (nvsALC), former-smoker (fsALC), and active smokers (asALC), over approximately 8 months of abstinence from alcohol. Methods: ALC participants were evaluated at approximately 1 month of abstinence (AP1; n=132) and reassessed after 8 months of sobriety (AP2; n=54). Never-smoking controls (CON; n=33) completed a baseline and follow-up (n=19) assessment approximately 9 months later. Domains evaluated were executive functions, general intelligence, processing speed, visuospatial skills and working memory; a domain composite was formed from the arithmetic average of the foregoing domains. nvsALC showed greater improvement than fsALC, asALC and CON on most domains over the AP1-AP2 interval. fsALC demonstrated greater recovery than asALC on all domains except visuospatial skills; fsALC also showed greater improvements than CON on general intelligence, working memory and domain composite. asALC did not show significant improvement on any domain over the AP1-AP2 interval. At 8 months of abstinence, asALC were inferior to CON and nvsALC on multiple domains, fsALC performed worse than nvsALC on several domains, but nvsALC were not different from CON on any domain. Our results provide robust evidence that smoking status influenced the rate and extent of neurocognitive recovery between 1 and 8 months of abstinence in this ALC cohort. Chronic smoking in AUD likely contributes to the considerable heterogeneity observed in neurocognitive recovery during extended abstinence. The findings provide additional strong support for the benefits of smoking cessation and the increasing clinical movement to offer smoking cessation resources concurrent with treatment for AUD.
  • Effects+of+Ethanol+on+Plasma+Ghrelin+levels+in+the+Rat+During+Early+and+Late+Adolescence&rft.title=Alcohol&rft.issn=0741-8329&">Effects of Ethanol on Plasma Ghrelin levels in the Rat During Early and
           Late Adolescence
    • Abstract: Publication date: Available online 7 January 2020Source: AlcoholAuthor(s): Kati L. Healey, Justine D. Landin, Kira Dubester, Sandra Kibble, Kristin Marquardt, Julianna N. Brutman, Jon F. Davis, H. Scott Swartzwelder, L. Judson ChandlerAbstractGhrelin is an appetite-regulating peptide that is primarily secreted by endocrine cells in the stomach and is implicated in regulation of alcohol consumption and alcohol-reinforced behaviors. In the present study, adolescent Sprague-Dawley rats received intermittent ethanol (AIE) exposure by intragastric intubation (5 g/kg) or vapor inhalation, manipulations conducted between postnatal days (PD) 28-43. On the first and last day of AIE exposure, the level of intoxication was examined 1 hr after ethanol gavage or upon removal from the vapor chamber. This was immediately followed by a blood draw for determination of the blood ethanol concentration (BEC) and plasma levels of acylated ghrelin (acyl-ghrelin; active). On PD 29, plasma levels of acyl-ghrelin were significantly elevated in male (but not female) rats in response to acute ethanol exposure by both gastric gavage and vapor inhalation. Importantly, assessment of plasma acyl-ghrelin in response to repeated ethanol exposure revealed a complex interaction of both sex and method of AIE exposure. On PD 43, vapor inhalation increased plasma acyl-ghrelin in both males and females compared to their air control counterparts, whereas there was no change in plasma levels of acyl-ghrelin in either male or female rats in response to exposure by intragastric gavage. Assessment of plasma acyl-ghrelin following a 30-day ethanol-free period revealed AIE exposure did not produce a change in basal levels. In addition, an acute ethanol challenge in adult rats of 5g/kg via gastric gavage had no effect on plasma ghrelin levels when assessed one hr after initiation of exposure. Collectively, these observations suggest that acyl-ghrelin, a primary gut-brain signaling hormone, is elevated by ethanol during early adolescence independent of administration route, and in gender-dependent fashion.
  • Alcohol consumption and cognitive function in elderly Japanese men
    • Abstract: Publication date: Available online 7 January 2020Source: AlcoholAuthor(s): Ali Tanweer Siddiquee, Aya Kadota, Akira Fujiyoshi, Naoko Miyagawa, Yoshino Saito, Harumitsu Suzuki, Keiko Kondo, Hiromi Yamauchi, Takahiro Ito, Hiroyoshi Segawa, Ikuo Tooyama, Katsuyuki Miura, Hirotsugu Ueshima, SESSA Research GroupAlthough heavy alcohol consumption has been identified as a risk factor for adverse cognitive functioning, it currently remains unclear whether moderate alcohol consumption exerts similar effects. Observational studies previously reported the potential benefits of moderate alcohol consumption on cognition, particularly in the elderly; however, these effects have not yet been demonstrated in Asian populations. The aim of the present study was to investigate the relationship between alcohol consumption levels and global and domain-specific cognitive functions in cognitively intact elderly Japanese men. Cross-sectional data from the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA), an ongoing prospective, population-based study in Shiga, Japan, were used to examine the relationship between alcohol consumption and cognitive function. Men (n = 585), aged ≥65 years, provided information on their weekly consumption of alcohol and the data obtained were used to construct categories of never, ex- (quit before interview), very light (23 - 46 g/day), and heavy (>46 g/day) drinkers. Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI). A fractional logistic regression model adjusted for age, education, body mass index, smoking, exercise, hypertension, diabetes, and dyslipidemia showed that the CASI scores for global and domain-specific cognitive functions were not significantly different between all subgroups of current drinkers and never-drinkers. However, the CASI score of ex-drinkers (multivariable adjusted mean CASI score [SD]) was significantly lower than that of never-drinkers in the global (never vs ex: 90.16 [2.21] vs 88.26 [2.58]) and abstraction and judgment domains (never vs ex: 9.48 [0.46] vs 8.61 [0.57]). The present results do not suggest any beneficial or adverse relationship between current alcohol consumption levels and cognitive functioning (both global and domain specific) in elderly Japanese men; however, low cognitive function among ex-drinkers warrants future investigations to identify the factors causing drinkers to quit.
  • Effects of chronic intermittent ethanol exposure and withdrawal on
           neuroblastoma cell transcriptome
    • Abstract: Publication date: Available online 7 January 2020Source: AlcoholAuthor(s): Jeanette N. McClintick, Kriti Thapa, Yunlong Liu, Xiaoling Xuei, Howard J. EdenbergAbstractCycles of heavy drinking and abstinence can lead to ethanol abuse disorder. We studied the effects of chronic intermittent ethanol exposure (CIE) over three weeks on neuroblastoma cells, using an ethanol concentration frequently attained in binge drinking (40 mM, 184 mg/dl). There were many changes in gene expression but most were small. CIE affected pathways instrumental in the development or plasticity of neurons, including axonal guidance, reelin signaling and synaptogenesis. Genes involved in dopamine and serotonin signaling were also affected. Changes in transporters and receptors could dampen both NMDA and norepinephrine transmissions. Decreased expression of the GABA transporter SLC6A11 could increase GABA transmission and has been associated with a switch from sweet drinking to ethanol consumption in rats. Ethanol increased stress responses such as unfolded protein response. TGF-β and NFκB signaling were increased. Most of the genes involved in cholesterol biosynthesis were decreased in expression. Withdrawal for 24 h after CIE caused most of the CIE-induced expression changes to move back toward unexposed levels.
  • In Vivo Two-Photon Imaging of Neuronal and Brain Vascular Responses in
           Mice Chronically Exposed to Ethanol
    • Abstract: Publication date: Available online 17 December 2019Source: AlcoholAuthor(s): Phillip O’Herron, Phillip M. Summers, Andy Y. Shih, Prakash Kara, John J. WoodwardAbstractThe effects of ethanol on brain function have been extensively studied using a variety of in vitro and in vivo techniques. For example, electrophysiological studies using brain slices from rodents and non-human primates have demonstrated that acute and chronic exposure to ethanol alters the intrinsic excitability and synaptic signaling of neurons within cortical and sub-cortical areas of the brain. In humans, neuroimaging studies reveal alterations in measures of brain activation and connectivity in subjects with alcohol use disorder. While complementary, these methods are inherently limited due to issues related to either disruption of normal sensory input (in vitro slice studies) or resolution (whole brain imaging). In the present study, we used 2-photon laser scanning microscopy in intact animals to assess the impact of chronic ethanol exposure on sensory evoked neuronal and vascular responses. Adult male C57BL/6J mice were exposed to 4 weekly cycles of chronic intermittent ethanol (CIE) exposure while control mice were exposed to air. After withdrawal (> 72 hr), a cranial window was placed over the primary visual cortex (V1) and sensory evoked responses were monitored using the calcium indicator OGB-1. CIE exposure produced small but significant changes in response amplitude (decrease) and orientation selectivity of V1 neurons (increase). While arteriole diameter did not differ between control and CIE mice under baseline conditions, sensory-evoked dilation was enhanced in vessels from CIE exposed mice as compared to controls. This was accompanied by a reduced latency in response to stimulation. In separate experiments, pial arteriole diameter was measured in the barrel cortex of control and CIE exposed mice. Baseline diameter of barrel cortex arterioles was similar between control and CIE exposed mice but unlike vessels in V1, sensory-evoked dilation of barrel cortex arterioles was similar between the two groups. Together the results of these studies suggest that chronic exposure to alcohol induces changes in neurovascular coupling that are region dependent.
  • Modulation of responses to visual stimulus onset and offset by chronic
           alcohol consumption and withdrawal in the rat visual cortex and lateral
           geniculate nucleus
    • Abstract: Publication date: Available online 13 December 2019Source: AlcoholAuthor(s): Redas Dulinskas, Osvaldas RuksenasIn the visual system chronic alcohol consumption and subsequent abstinence strongly modulate processing of sensory information, which could interfere with the actions in our daily life. Although previous studies showed histological and electrophysiological changes in the retina and visual cortex during chronic alcohol consumption and abstinence, there is still a lack of information related to the effect of alcohol on: 1) different stages of visual information processing; 2) responses of stimulus onset (ON) and offset (OFF). In order to answer these questions we recorded visual evoked potentials (VEPs), elicited by onset and offset of 500 ms stimulus, following long-term alcohol consumption (8 weeks) and abstinence (3 weeks) in freely moving Wistar rats. Latency and amplitude of five components in the visual cortex (N1VC, P2VC, N2VC, P3VC, N3VC) and three components in the lateral geniculate nucleus (P1LGN, N1LGN, P2LGN) were analyzed. The results showed that long-term chronic alcohol consumption and abstinence have a strong long-term and, in some cases, irreversible impact on the visual information processing. Both of these conditions modulate only the last stage of stimulus onset processing at the level of visual cortex, but not at the level of lateral geniculate body. Response to the stimulus offset is more susceptible to the effect of alcohol consumption and/or abstinence and is modulated at both, visual cortex and lateral geniculate nucleus, levels. This modulation at different stages of information processing chain can result in inaccurate processing of visual stimuli parameters and can lead to changes in perception of stimulus duration and intensity.
  • School and town factors associated with risky alcohol consumption among
           Catalan adolescents
    • Abstract: Publication date: February 2020Source: Alcohol, Volume 82Author(s): Núria Obradors-Rial, Carles Ariza, Xavier Continente, Carles MuntanerAbstractRisky alcohol consumption among adolescents has health and social consequences. Evidence identifying the school context that determines alcohol consumption among rural and urban adolescents is lacking. This study aimed to describe the contextual school and town factors determining risky alcohol consumption among rural and urban 10th-grade adolescents (15–17 years old) from Catalonia (northeastern Spain). The study had a cross-sectional design. Cluster sampling with the class as the sampling unit was used, and a total of 1268 10th-grade adolescents from Catalonia nested in 26 high schools participated in the study. A computerized and self-administrated questionnaire was used to collect individual variables. Contextual variables were collected from the Catalan police registers, geocoded sources, and governmental internet databases, and by aggregation of answers from the self-administrated questionnaire. The prevalence of risky alcohol consumption was calculated, and a multilevel Poisson regression analysis with robust variance was conducted with data from adolescents nested within high schools. The results show that risky alcohol consumption is higher among rural adolescents (59.3%) than among urban youth (51.1%) (p 
  • Acute alcohol consumption alters the peripheral cytokines IL-8 and
    • Abstract: Publication date: Available online 20 November 2019Source: AlcoholAuthor(s): Ansel T. Hillmer, Haleh Nadim, Lesley Devine, Peter Jatlow, Stephanie S. O’MalleyAbstractBackgroundAcute alcohol triggers release of cytokines, which are immune signaling molecules. Dysregulated cytokine levels are associated with impaired immune function, and peripheral cytokine levels may communicate with the brain to propagate drinking-related behaviors. This exploratory study aims to characterize the peripheral cytokine response to an alcohol challenge in a well-controlled laboratory setting.MethodsModerate alcohol drinkers (n=17), abstinent for>5 days, consumed alcohol calibrated to achieve blood concentrations of 120 mg/dL. Serum cytokine levels (IL-6, IL-8, IL-12, IFN-γ, TNF-α) were measured prior to drinking, 6 hours after drinking, and 24 hours after drinking. Linear mixed models evaluated within-subject differences in cytokine levels over time.ResultsThe pro-inflammatory chemokine IL-8 significantly increased 6 hours after alcohol (F(1,34)=4.13, p=0.0002, d’=0.5). In contrast, the pro-inflammatory cytokine TNF-α significantly decreased 6 hours after alcohol (F(1,34)=-3.07, p=0.004, d’=0.3). No cytokines were significantly different from baseline 24 hours after alcohol.ConclusionsIn our exploratory data, acute alcohol challenge (120 mg/dL) elicits dynamic changes in the pro-inflammatory molecules IL-8 and TNF-α. The findings help inform the temporal profile of cytokine response to alcohol, and identify IL-8 as a cytokine of interest for future studies of periphery-brain immune communication.
  • Age-dependent impairment of metabotropic glutamate receptor 2-dependent
           long-term depression in the mouse striatum by chronic ethanol exposure
    • Abstract: Publication date: February 2020Source: Alcohol, Volume 82Author(s): Kari A. Johnson, Daniel J. Liput, Gregg E. Homanics, David M. LovingerAbstractChronic alcohol exposure is associated with increased reliance on behavioral strategies involving the dorsolateral striatum (DLS), including habitual or stimulus-response behaviors. Presynaptic G protein-coupled receptors (GPCRs) on cortical and thalamic inputs to the DLS inhibit glutamate release, and alcohol-induced disruption of presynaptic GPCR function represents a mechanism by which alcohol could disinhibit DLS neurons and thus bias toward use of DLS-dependent behaviors. Metabotropic glutamate receptor 2 (mGlu2) is a Gi/o-coupled GPCR that robustly modulates glutamate transmission in the DLS, inducing long-term depression (LTD) at both cortical and thalamic synapses. Loss of mGlu2 function has recently been associated with increased ethanol seeking and consumption, but the ability of alcohol to produce adaptations in mGlu2 function in the DLS has not been investigated. We exposed male C57Bl/6J mice to a 2-week chronic intermittent ethanol (CIE) paradigm followed by a brief withdrawal period, then used whole-cell patch clamp recordings of glutamatergic transmission in the striatum to assess CIE effects on mGlu2-mediated synaptic plasticity. We report that CIE differentially disrupts mGlu2-mediated long-term depression in the DLS vs. dorsomedial striatum (DMS). Interestingly, CIE-induced impairment of mGlu2-LTD in the dorsolateral striatum is only observed when alcohol exposure occurs during adolescence. Incubation of striatal slices from CIE-exposed adolescent mice with a positive allosteric modulator of mGlu2 fully rescues mGlu2-LTD. In contrast to the 2-week CIE paradigm, acute exposure of striatal slices to ethanol concentrations that mimic ethanol levels during CIE exposure fails to disrupt mGlu2-LTD. We did not observe a reduction of mGlu2 mRNA or protein levels following CIE exposure, suggesting that alcohol effects on mGlu2 occur at the functional level. Our findings contribute to growing evidence that adolescents are uniquely vulnerable to certain alcohol-induced neuroadaptations, and identify enhancement of mGlu2 activity as a strategy to reverse the effects of adolescent alcohol exposure on DLS physiology.
  • Acute alcohol consumption-induced let-7a inhibition exacerbates hepatic
           apoptosis by regulating Rb1 in mice
    • Abstract: Publication date: Available online 14 November 2019Source: AlcoholAuthor(s): Jeong Hoon Pan, Hyunjin Kim, Jingsi Tang, Kaleigh E. Beane, Jeen-Woo Park, Seongbae Kong, Byungwhi C. Kong, Young Jun Kim, Eui-Cheol Shin, Jun Ho Kim, Jiangchao Zhao, Jin Hyup Lee, Jae Kyeom KimAbstractAlcohol consumption is a critical risk factor for hepatic pathogenesis, including alcoholic liver diseases (ALD), but implications of alcohol-induced dysregulation of microRNA (miRNA) in ALD pathogenesis are not completely understood. In the present study, C57BL/6J male mice were treated with saline (CON; oral gavage; n=8) or alcohol (EtOH; 3 g/kg·body weight; oral gavage; n=8) for seven days. A total of 599 miRNAs and 158 key mRNAs related to fatty liver and hepatotoxicity pathways were assessed in mice liver tissues. The mRNA expression datasets were then utilized to predict interactions with miRNAs that were changed by alcohol consumption. Predicted miRNA-mRNA interactions were validated using in vitro miRNA transfection experiments. As results, let-7a was significantly decreased in the EtOH group and Rb1 mRNA was predicted as a target gene, this was further supported by an inverse correlation of RB1 and let-7a expression in mice liver tissue. Additionally, key protein expressions involved in RB1-apoptosis axis [i.e., p73, cleaved CASP-3 (cCASP-3), and cCASP-7] showed a trend of increase in the EtOH mice; this was also confirmed by capase-3 enzyme activity and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay in alcohol consumed mice liver. In line with our in vivo observations, alcohol treatment suppressed the let-7a expression and subsequently upregulated p73, cCASP-3, and cCASP-7 protein expressions in mice hepatocytes. Additional proteins in apoptosis regulatory pathway (i.e., MDM2-p53 axis) were significantly changed in response to let-7a suppression in the cells. Taken together, the current study provides mechanistic evidence that alcohol consumption induced let-7a suppression results in the upregulation of RB1, thereby promoting hepatic apoptosis through induction of pro-apoptotic proteins (e.g., p73), and through, at least in part, preventing MDM2-mediated p53 degradation.
  • Co-existence of ethanol-related respiratory and motivational learning
           processes based on a tactile discrimination procedure in neonatal rats
    • Abstract: Publication date: Available online 14 November 2019Source: AlcoholAuthor(s): G. D’aloisio, M.B. Acevedo, A.F. Macchione, F. Anunziata, J.C. MolinaAbstractIn rats, high ethanol doses during early postnatal life exert deleterious effects upon brain development that impact on diverse social and cognitive abilities. This stage in development partially overlaps with the 3rd human gestational trimester commonly referred as the brain growth spurt period. At this stage in development human fetuses and rat neonates (postnatal days 3-9) exhibit relatively high respiratory rates that are affected by subteratogenic ethanol doses. Recent studies suggest conditioned breathing responses in the developing organism given explicit associations between exteroceptive stimuli and the state of EtOH intoxication. Furthermore, studies performed with near term rat fetuses suggest heightened sensitivity to EtOH’s motivational effects. The present study was meant to analyze the unconditioned effects of EtOH intoxication and the possible co-occurrence of learning mechanisms that can impact upon respiratory plasticity and preference for cues that signal the state of intoxication as well as the effects of the drug related with motor stimulation. Neonatal rats were subjected to differential experiences with salient tactile cues explicitly paired or not with the effects of vehicle or EtOH (2.0 g/kg). A tactile discrimination procedure applied during PDs 3, 5, 7 and 9 allowed to identify the emergence of EtOH-derived non-associative and associative learning processes that affect breathing plasticity; particularly when considering apneic disruptions. Ethanol was found to partially inhibit these disruptions that appeared to be intimately related with stressful circumstances defined by the experimental procedure. Tactile cues paired with the drug’s effects were also observed to exert an inhibitory effect upon these breathing disruptions. The level of contingency between a given tactile cue and EtOH intoxication also resulted in significant changes in the probability of seeking this cue in a tactile preference test. In addition, the state of intoxication exerted motor stimulating effects. When contrasting the data obtained via the analysis of the different dependent variables it appears that most EtOH-derived changes are modulated by positive and/or negative (antianxiety) reinforcing effects of the drug. As a whole, the study indicates co-existence of EtOH-related functional changes in the developing organism that simultaneously affect respiratory plasticity and preference patterns elicited by stimuli that signal EtOH’s motivational effects. These results emphasize the need to consider significant alterations due to minimal EtOH experiences that argue against “safe” levels of exposure in a critical stage in brain development.
  • Repeated ethanol exposure influences key enzymes in cholesterol and lipid
           homeostasis via the AMPK pathway in the rat prefrontal cortex
    • Abstract: Publication date: Available online 14 November 2019Source: AlcoholAuthor(s): Shijie Xu, Se Jin Jeong, Gang Li, Ja Wook Koo, Ung Gu KangAbstractCholesterol homeostasis has been proposed to be implicated in the development of addiction. However, the effects of ethanol on cholesterol homeostasis within the brain are not well understood. One of the most important regulators of cholesterol homeostasis is HMG-CoA reductase (HMG-CoAR), the rate-limiting enzyme of cholesterol biosynthesis. We examined the phosphorylation of HMG-CoAR and the other key regulator of lipid synthesis, acetyl-CoA carboxylase (ACC), following acute or chronic treatment with ethanol (0.5, 1, or 2 g/kg) in the rat prefrontal cortex. The phosphorylation of AMP-activated protein kinase (AMPK), which regulate the HMG-CoAR activity, and its well-known upstream regulators were also studied. The phosphorylation of HMG-CoAR and ACC were transiently increased by ethanol treatment only in animals previously treated chronically with ethanol. Acute administration to naïve animals did not induce the phosphorylation, regardless of dosage. Similarly, the phosphorylation of AMPK and the upstream regulators, LKB1 and CaMK4, were transiently increased only in chronically ethanol-treated animals. In naïve animals, a high dose (2 g/kg) of ethanol decreased phosphorylation. The phosphorylation of TAK1, another upstream kinase of AMPK was increased only from 30 min to 24 h after the chronic treatment with ethanol. Together, these results indicate that repeated exposure is required for the activating effect of ethanol on HMG-CoAR and ACC. This effect seems to be mediated by the AMPK system, and may contribute to the long-lasting neuroadaptation involved in the development of alcohol dependence.
  • Maternal Iron Nutriture Modulates Placental Development in a Rat Model of
           Fetal Alcohol Spectrum Disorder
    • Abstract: Publication date: Available online 14 November 2019Source: AlcoholAuthor(s): Sze Ting (Cecilia) Kwan, Camille A. Kezer, Kaylee K. Helfrich, Nipun Saini, Shane M. Huebner, George R. Flentke, Pamela J. Kling, Susan M. SmithAbstractPrenatal alcohol exposure (PAE) causes developmental abnormalities known as fetal alcohol spectrum disorder (FASD). Maternal iron status modulates the severity of these defects in the offspring. Because the placenta is central in supporting fetal development, we investigated if maternal iron status similarly modulates alcohol’s effects in the placenta. We hypothesized that PAE causes placental insufficiency by decreasing placental weight and efficiency, and these are worsened by maternal iron deficiency (ID) and alleviated by dietary iron-fortification (IF). We also determined whether altered placental iron flux and inflammatory balance contribute to placental insufficiency. Pregnant Long-Evans rats consumed an ID (2-6 ppm), iron-sufficient (IS; 100 ppm), or IF (500 ppm) diet. Alcohol (5g/kg body weight) or isocaloric maltodextrin (MD) was gavaged daily from gestational day (GD) 13.5-19.5. Placental outcomes were evaluated on GD20.5. PAE reduced fetal weight (P < 0.0001), placental weight (P = 0.0324), and placental efficiency (P = 0.0043). PAE downregulated placental transferrin receptor (P = 0.0032); it also altered placental Il1b and Tnf expression and Il6:Il10 ratio (P = 0.0337, 0.0300 and 0.0034, respectively) to generate a response favoring inflammation. ID-PAE further reduced fetal growth and placental efficiency and induced a heightened pro-inflammatory placental profile. IF did not rescue the alcohol-reduced fetal weight, but it normalized placental efficiency and decreased placental inflammation. These placental cytokines correlated with fetal and placental growth, and explained 45% of variability in fetal weight and 20% of variability in placental efficiency. In summary, alcohol induces placental insufficiency and is associated with a pro-inflammatory cytokine profile exacerbated by maternal ID and mitigated by maternal IF. Because the placenta is closely linked to intrauterine growth, the placental insufficiency reported here may correlate with the lower birth weights in a subgroup of individuals who experienced PAE.
  • Interaction effect of alcohol consumption and Alzheimer disease polygenic
    • Abstract: Publication date: Available online 14 November 2019Source: AlcoholAuthor(s): William J. Matloff, Lu Zhao, Kaida Ning, David V. Conti, Arthur W. TogaAbstractAlcohol consumption and genetic risk for Alzheimer disease (AD) are among many factors known to be associated with brain structure in cognitively healthy adults. It is unclear, however, whether the effect of alcohol consumption on brain structure varies depending on a person’s level of genetic risk for AD. We hypothesized that there is an interaction effect of alcohol consumption and a 33-SNP AD polygenic risk score (PRS) on the cortical thickness of brain regions known to be affected early in the course of AD. Studying 6213 cognitively healthy subjects from the UK Biobank, we found a significant interaction effect of the 33-SNP AD PRS and alcohol consumption on this AD Cortical Thickness Signature. Stratified, among those who consume 12-24 g/day of alcohol, the 33-SNP AD PRS had a significant, positive association with AD Cortical Thickness Signature, with high risk subjects having the greatest AD Cortical Thickness Signature. There were no significant associations of the 33-SNP AD PRS with AD Cortical Thickness Signature among the nondrinker or 48 g/day groups. It is unclear whether this interaction is due to a detrimental or beneficial effect of moderate alcohol consumption in those with the highest genetic risk for AD.
  • Effects of the hallucinogenic beverage ayahuasca on voluntary ethanol
           intake by rats and on cFos expression in brain areas relevant to drug
    • Abstract: Publication date: Available online 4 November 2019Source: AlcoholAuthor(s): Luciana Marangni Nolli, Danilo Gustavo Rodrigues de Oliveira, Stefany Sousa Alves, Marcus Vinicius von Zuben, Aline Pic-Taylor, Marcia Renata Mortari, Eloisa Dutra CaldasAbstractAyahuasca is a hallucinogenic infusion used in religious ritualsthat has serotoninergic properties and may be a potential therapeutic option for drug addiction. In this study, Wistar rats had intermittent access to ethanol for 8 weeks, receiving water (control), naltrexone (NTX, 2 mg/kg pc ip) or ayahuasca (Aya) at 0.5, 1 or 2X the ritual dose in the final 5 days. A naïve group had only access to water. Ethanol intake was estimated throughoutthe experimentand cFos expression was evaluated in medial orbital cortex (MO), ventral orbital (VO), lateral orbital (LO), nucleus accumbens (NAc) and striatum. Treatment with either NTX or Aya (oral) did not decrease ethanol intake compared to the baseline level (5th to 7th week), but the NTX group intake was significantly lower than control (p< 0.05). Ethanol significantly increased cFos expression in the MO region for control (p < 0.0001), NTX (p< 0.05), Aya1 (p
  • Ethanol-Paired Stimuli Can Increase Reinforced Ethanol Responding
    • Abstract: Publication date: Available online 2 November 2019Source: AlcoholAuthor(s): R.J. Lamb, Charles W. Schindler, Brett C. GinsburgAbstractWhile ethanol-paired stimuli are frequently postulated to increase drinking motivation and thus increase ethanol-responding and precipitate relapse, no study has demonstrated increases in ethanol-reinforced responding following presentation of an ethanol-paired stimulus that had not previously been part of a contingent relationship. Previous studies have shown that food-paired stimuli can increase food-responding that is at low rates and increase food consumption in food-sated rats. In Experiment 1, we show that an ethanol-paired stimulus can increase ethanol responding that is at low levels late in the experimental session, presumably due to satiation. However, these increases may have resulted from either associative or non-associative mechanisms. In Experiment 2, we compared the effects of an ethanol-paired stimulus to those of the same stimulus in a Truly-Random-Control group. In a Truly-Random-Control, the stimulus and ethanol each are presented on independent random schedules, and thus any differences between the effects of the stimulus in the experimental and control groups is likely attributable to the association between the stimulus and ethanol. The stimulus increased ethanol-reinforced responding in both the experimental and control groups, but these increases were greater in the experimental than the control group. Thus, both stimulus-change and the pairing of the stimulus with ethanol may result in increases in ethanol-reinforced responding.
  • A Nationwide Randomised, Double-Blind, Placebo-Controlled Physicians’
           Trial of Loxoprofen for the Treatment of Fatigue, Headache, and Nausea
           after Hangovers
    • Abstract: Publication date: Available online 2 November 2019Source: AlcoholAuthor(s): Masahiko Hara, Kenichi Hayashi, Tetsuhisa Kitamura, Michitaka Honda, Masatake TamakiAbstractHangovers are associated with negative economic consequences due to decreased job performance or frequent visits to physicians. Thus, a new strategy for the alleviation of hangover-related symptoms is needed to avoid this detriment to the society. The purpose of this nationwide randomised, double-blind, placebo-controlled physicians’ trial was to evaluate the efficacy of loxoprofen sodium for the alleviation of fatigue, headache, and nausea after hangover. A total of 229 participants were randomised to receive loxoprofen sodium (60 mg once orally) or placebo. The study was closed when the first 150 participants (n = 74 in the loxoprofen vs. n = 76 in the placebo groups) experienced hangovers. The primary endpoint was set as the difference in severity of general fatigue before and 3 hours after taking the test drugs and was evaluated using a visual analogue scale. Secondary endpoints included difference in severity of headache, nausea, and incidence of adverse events. The study participants were 34 (interquartile range; 30–39) years old, 92.0% were men, and both groups were comparable for baseline characteristics. The alleviation of general fatigue did not differ statistically between the loxoprofen and placebo groups (24 [14–49] vs. 19 [9–35], p = 0.07). However, the alleviation of headache was statistically greater in the loxoprofen group (25 [10–50] vs. 10 [2–30], adjusted difference 14, 95% confidence interval 8–21, p < 0.001), whereas, there was no difference in nausea (7 [0–27] vs. 10 [0–24], p = 0.68). The incidence of adverse symptoms such as epigastric discomfort was also comparable between groups (2.7% vs. 3.9%, p = 0.25). Loxoprofen sodium was effective for relieving headaches after hangovers but did not alleviate general fatigue or nausea.
  • Plasma cytokine levels in patients with chronic alcohol overconsumption:
           relations to gut microbiota markers and clinical correlates
    • Abstract: Publication date: Available online 11 October 2019Source: AlcoholAuthor(s): Steinar Traae Bjørkhaug, Sudan Prasad Neupane, Jørgen G. Bramness, Håvard Aanes, Viggo Skar, Asle W. Medhus, Jørgen ValeurAbstractBackgroundAlcohol-related morbidity may involve changes in the gut microbiota and immune dysregulation. We have previously demonstrated alterations in gut microbiota composition and functions in patients with alcohol overconsumption, and now aimed to investigate possible associations between cytokine levels, gut microbiota and clinical symptoms.MethodsWe included hospital inpatients with a history of chronic alcohol overconsumption. For comparison, we included control patients with a low alcohol intake. Cytokine levels (TGF-β1, TNF-α, IL-10, IL-8, IL-6, IFN-γ, MCP-1, IL-1RA, IL-1β and IL-17) were determined using a customized V-plex assay. We then examined associations of cytokine levels with the abundance of Proteobacteria and Faecalibacterium, percentage of the short-chain fatty acid butyrate, psychiatric symptoms (Hospital Anxiety and Depression Scale) and biochemical liver variables.ResultsWe included 28 patients with alcohol overconsumption (79% men), and 25 control patients (72% men). Patients with alcohol overconsumption had higher levels of IL-6 (p = 0.002), IFN-γ (p = 0.018) and MCP-1 (p = 0.006), and lower levels of TGF-β1 (p = 0.017) compared with control patients. Inverse correlations were found between Proteobacteria abundance and TNF-α (Rs = -0.55, p = 0.02) and IL-8 (Rs = -0.58, p = 0.014), and between Faecalibacterium and MCP-1 levels (Rs = -0.56, p = 0.02) in the control patients, but not in patients with alcohol overconsumption. Patients with alcohol overconsumption reported more psychiatric symptoms, and these symptoms were inversely correlated with IL-10 levels. There were positive correlations between several of the assessed cytokines and biochemical liver variables, and negative correlations between cytokine levels and albumin.ConclusionPatients with alcohol overconsumption had a cytokine profile suggestive of increased systemic inflammatory activity, with higher levels of pro-inflammatory cytokines (IL-6, IFN-γ and MCP-1) and lower levels of anti-inflammatory cytokines (TGF-β1). The findings may represent a link between alcohol use and alcohol-related morbidity.
  • Corrigendum to < Repetitive transcranial magnetic stimulation: Re-wiring
           the alcoholic human brain>
    • Abstract: Publication date: Available online 10 October 2019Source: AlcoholAuthor(s): Diana M, Bolloni C, Antonelli M, Di Giuda D, Cocciolillo F, Fattore L, Addolorato G
  • Are hazardous drinkers more impulsive than light drinkers' A
           comprehensive assessment in young adults
    • Abstract: Publication date: Available online 30 September 2019Source: AlcoholAuthor(s): Matthew J. Mayhew, James M. Byrne, Jane H. Powell, Tim MeynenAbstractThose with alcohol dependence are characteristically impulsive. It is unclear whether the same is true of hazardous drinkers (i.e. women routinely drinking more than 14 units in a typical week but less than 35, and men drinking more than 14 units but less than 50). Yet it is important to understand the mechanisms involved in such drinking, since it places the drinker at risk for future harm. The present study thus comprehensively assessed whether impulsivity was elevated in hazardous drinkers, compared to lighter drinkers. An opportunity sample of 57 light and 49 hazardous drinkers were assessed on the following impulsivity sub-domains (via the measures in parentheses): (i) trait impulsivity (the Barratt Impulsiveness Scale, Version 11); (ii) temporal impulsivity (the Monetary Choice Questionnaire); (iii) stopping impulsivity (the Stop-Signal Task); (iv) waiting impulsivity (the Continuous Performance Task or CPT); (v) reward-sensitivity (the Behavioural Activation Scales); and (vi) risk-taking (the Balloon Analogue Risk Task). Alcohol- and other drug-dependent individuals were excluded from the study, whilst socio-demographics (age, gender and socio-economic status), mood, binge-drinking and nicotine intake were all controlled for. The groups were compared via a series of Bonferroni-corrected, independent-measures t-tests. The results revealed that hazardous drinkers were more impulsive than light drinkers on the CPT; there were no other statistically significant group differences. Consistent with the above, a logistic regression, with drinking group as the dependent variable and the impulsivity indices as independent variables, revealed that only CPT performance was a significant predictor of drinking status. Other than gender, none of the control variables significantly correlated with CPT performance. A sequential linear regression revealed that drinking status continued to predict CPT performance, after first accounting for gender. Thus, from a battery of impulsivity measures, only waiting impulsivity (i.e. CPT score) was elevated in hazardous drinkers, relative to lighter drinkers. Waiting impulsivity may thus be important in the maintenance of hazardous drinking.
  • Differential patterns of alcohol and nicotine intake: Combined alcohol and
           nicotine binge consumption behaviors in mice
    • Abstract: Publication date: Available online 23 September 2019Source: AlcoholAuthor(s): Margot C. DeBaker, Jenna M. Robinson, Janna K. Moen, Kevin Wickman, Anna M. LeeAbstractLate adolescence and young adulthood, corresponding to the high school and college years, are vulnerable periods for increased alcohol and nicotine use. The dramatic increase in the prevalence of electronic cigarette use is particularly concerning in these age groups. Late adolescents and young adults are more likely to engage in cycles of binge drug consumption, and alcohol and nicotine are frequently used together. However, there is little data examining the combination of alcohol and nicotine in binge models in animal models. In this study, our objectives were to determine how voluntary nicotine consumption beginning in late adolescence influenced subsequent binge alcohol consumption in young adulthood, how a combination of alcohol and nicotine binge consumption differed from alcohol-only binge consumption, and whether nicotine would be consumed when presented in a binge procedure. Male C57BL/6J mice voluntarily consumed unsweetened alcohol and nicotine in continuous access bottle choice procedures in combination with cycles of drinking-in-the-dark. Our results show that experience with voluntary nicotine consumption in late adolescence did not affect subsequent binge alcohol consumption in early adulthood. However, mice that consumed nicotine in adolescence showed an initial decrease in alcohol preference, and consequently increase in nicotine preference, on the first session of combined ethanol and nicotine binge consumption in adulthood compared with mice that drank only water during late adolescence. Lastly, we found that mice readily consumed unsweetened nicotine when presented in a binge procedure, and the level of consumption exceeded the nicotine consumption observed in the combination alcohol and nicotine binge. Our data show that expansion of the patterns of alcohol and nicotine co-consumption in mouse models is possible, which will enable us to dissect relevant molecular targets underlying these consumption patterns and better inform drug development efforts.
  • Alcohol preferring P rats exhibit aversion resistant drinking of alcohol
           adulterated with quinine
    • Abstract: Publication date: Available online 19 September 2019Source: AlcoholAuthor(s): Nicholas M. Timme, David Linsenbardt, Maureen Timm, Taylor Galbari, Ethan Cornwell, Christopher LapishAbstractUnderstanding why some people continue to drink alcohol despite negative consequences and others do not is a central problem in the study of alcohol use disorder (AUD). In this study, we used alcohol preferring P rats (a strain bred to prefer to drink alcohol, a model for genetic risk for AUD) and Wistars (control) to examine drinking despite negative consequences in the form of an aversive bitter taste stimuli produced by quinine. Animals were trained to consume 10% ethanol in a simple Pavlovian conditioning task that paired alcohol access with an auditory stimulus. When the alcohol was adulterated with quinine (0.1 g/L), P rats continued to consume alcohol+quinine at the same rate as unadulterated alcohol, despite a demonstrated aversion to quinine adulterated alcohol when given a choice between adulterated and unadulterated alcohol in the home cage. Conversely, Wistars decreased consumption of quinine adulterated alcohol in the task, but continued to try the alcohol+quinine solution at similar rates to unadulterated alcohol. These results indicate that following about 8 weeks of alcohol consumption P rats exhibit aversion resistant drinking. This model could be used in future work to explore how biological basis of alcohol consumption and genetic risk for excessive drinking lead to drinking that is resistant to devaluation.
  • Evoked K-complexes and Altered Interaction Between the Central and
           Autonomic Nervous Systems during Sleep in Alcohol Use Disorder
    • Abstract: Publication date: Available online 17 September 2019Source: AlcoholAuthor(s): Adrian R. Willoughby, Massimiliano de Zambotti, Fiona C. Baker, Ian M. ColrainAbstractThere is evidence for impairment in both central nervous system (CNS) and autonomic nervous system (ANS) function with prolonged alcohol use. While these impairments persist into abstinence, partial recovery of function has been demonstrated in both systems during sleep. To investigate potential ANS dysfunction associated with cortical CNS responses (impairment in CNS-ANS coupling), we assessed phasic heart rate (HR) fluctuation associated with tones that did and those that did not elicit a K-complex (KC) during stable N2 non-rapid eye movement (NREM) sleep in a group of 16 recently abstinent alcohol use disorder (AUD) patients (41.6±8.5 years) and a group of 13 sex- and age-matched control participants (46.6±9.3 years). Electroencephalogram (EEG) and electrocardiogram (ECG) were recorded throughout the night. Alcohol consumption questionnaires were also administered to the AUD patients. AUD had elevated HR compared to controls at baseline prior to tone presentation. The HR fluctuation associated with KCs elicited by tone presentation was significantly smaller in amplitude, and tended to be delayed in time, in the AUD group compared with the control group, and the subsequent deceleration was also smaller in AUD. In both groups the increase in HR was larger and occurred earlier when KCs were produced than when they were not and there was no difference in the magnitude of the KC effect between groups. Phasic HR changes associated with KCs elicited by tones are impaired in AUD participants, reflecting ANS dysfunction possibly caused by an alteration of cardiac vagal trafficking. However, only the timing of the HR response was found to relate to estimated lifetime alcohol consumption in AUD. The clinical meaning and implications of these novel findings need to be determined.
  • Association between alcohol consumption and hypertension in Chinese
           adults: findings from the CHNS
    • Abstract: Publication date: Available online 13 September 2019Source: AlcoholAuthor(s): Fanfan Zhao, Qingqing Liu, Yuanjie Li, Xiaojie Feng, Hong Chang, Jun LyuAbstractObjectivesTo obtain information about alcohol consumption (henceforth “drinking”) among Chinese adults from 1991 to 2011, and to explore the association between drinking behavior and hypertension.MethodsAccording to the longitudinal data obtained in the China Health and Nutrition Survey (1991–2011), 50013 records of 12577 adults were selected by applying eligibility criteria. Chi-test was employed to explore the association between drinking and hypertension, by considering the frequency of drinking, daily alcohol intake, alcohol type, and the prevalence of hypertension. A multilevel logistic regression model was used to analyze the longitudinal association between drinking frequency and the prevalence of hypertension.ResultsThe prevalence of hypertension was higher in participants with a high drinking frequency than those with a low drinking frequency among both males and females (P
  • Consequences Of Alcohol Use, And Its Association With Psychological
           Distress, Sensitivity To Emotional Contagion And Age Of Onset Of Alcohol
           Use, In Uruguayan Youth With Or Without College Degree
    • Abstract: Publication date: Available online 11 September 2019Source: AlcoholAuthor(s): Paul Ruiz, Angelina Pilatti, Ricardo M. PautassiAbstractPsychological distress can promote alcohol consumption during emerging adulthood. Still unknown is, however, how predisposition to emotional contagion alters psychological distress, and how these phenomena are affected by level of education. The present study analyzed the effect of psychological distress, age of first contact with alcohol (early, late), and predisposition to emotional contagion on alcohol-induced negative consequences and on the volume of alcohol consumed during the last year. We also described alcohol-use behaviors as a function of sex, maximum level of education and age of first contact with alcohol, in 1505 youth from Uruguay (18-30 years). A survey measured alcohol use (Alcohol Use Disorders Identification Test and ad-hoc questionnaire), negative consequences of alcohol use [young adult alcohol consequences questionnaire (YAACQ)], psychological distress (Kessler scale) and proclivity to emotional contagion (Doherty Emotional contagion scale). The patterns of alcohol use were greater in men vs. women and in those featuring an early age of first alcohol use, yet similar in college and non-college graduates. Early drinkers had greater levels of psychological distress than late-onset drinkers. There was a significant bivariate and multiple correlation between psychological distress and the number of negative consequences of alcohol experienced during the last year, which remained significant even after controlling for total volume of alcohol consumed. Significant associations emerged between YAACQ scores and frequency of heavy episodic or binge drinking, and between psychological distress and emotional contagion, but not between emotional contagion and any of the remaining variables. Psychological distress was not significantly correlated with heavy episodic or binge drinking. The study indicates that, during adolescence and youth, psychological distress is associated with experiencing negative consequences of alcohol consumption. The study also suggested that greater levels of psychological distress may underlie the facilitating effect of an early age of drinking onset upon alcohol drinking patterns.
  • Inhibitory Influence of Agmatine in Ethanol Withdrawal-Induced Depression
           in Rats: Behavioral and Neurochemical Evidences
    • Abstract: Publication date: Available online 11 September 2019Source: AlcoholAuthor(s): Niyamat Chimthanawala, Shruti Patil, Rishabh Agrawal, Nandkishor R. Kotagale, Milind J. Umekar, Brijesh G. TaksandeAbstractAlthough ethanol withdrawal depression is one of the prominent reasons for its reinstatement and dependence, its neurochemical basis is not clearly understood. Present study investigated the role of agmatinergic system in ethanol withdrawal-induced depression using forced swim test (FST) in rats. Chronic exposure of animals to ethanol for 21 days and its abrupt withdrawal produced depression like behavior as evidenced by increased immobility time in FST, compared to the pair-fed control animals. The ethanol withdrawal-induced depression was significantly attenuated by agmatine (20-40 μg/rat, i.c.v.), moxonidine (50 μg/rat, i.c.v.), 2-BFI (20 μg/rat, i.c.v.), L-arginine (80 μg/rat, i.c.v.), amino-guanidine (25 μg/rat, i.c.v.) and arcaine (50 μg/rat, i.c.v.) by their once daily administration during the withdrawal phase (Day 21, 22 and 23). The antidepressant effect of agmatine in ethanol withdrawn rats was potentiated by imidazoline receptor I1 agonist, moxonidine (25 μg/rat, i.c.v.) and imidazoline receptor I2 agonist 2-BFI (10 μg/rat, i.c.v.) at their sub-effective doses. On the other hand, it was completely blocked by imidazoline receptor I1 antagonist, efaroxan (10 μg/rat, i.c.v.) and imidazoline receptor I2 antagonist, idazoxan (4 μg/rat, i.c.v.). In addition, agmatine levels were significantly reduced in brain samples of ethanol withdrawn rats as compared to the pair-fed control animals. In conclusion, the present study suggests the importance of endogenous agmatinergic system and imidazoline receptors system in ethanol withdrawal-induced depression. The data projects agmatine as a potential therapeutic target for the alcohol withdrawal-induced depression.
  • Home-detoxification and relapse prevention for alcohol dependence in low
           resource settings: an exploratory study from Goa, India.
    • Abstract: Publication date: Available online 29 August 2019Source: AlcoholAuthor(s): Abhijit Nadkarni, Richard Velleman, Urvita Bhatia, Godwin Fernandes, Ethel D’souza, Pratima MurthyAbstractDespite the increasing burden of alcohol dependence, treatment resources in low- and middle-income countries such as India, are concentrated in poorly accessible tertiary care facilities. The aim of our study was to examine the feasibility and acceptability of lay health worker delivered home-based packages of care for alcohol dependence. We conducted an uncontrolled treatment cohort with alcohol dependent adult males recruited in primary and secondary care. Lay health workers delivered home-detoxification and/or relapse prevention counselling. Process data was analysed using descriptive statistics. 11 men with alcohol dependence received home detoxification and relapse prevention counselling and 27 received only relapse prevention counselling. Of the 11 receiving home detoxification, one participant re-started drinking; all the rest safely completed the home detoxification. During detoxification, the pulse, blood pressure and temperature remained within the normal range and ataxia, dehydration, disorientation, sleep normalised over the course of the detoxification. Of the 38 who entered relapse prevention treatment, 15 (39.5%) completed treatment or had a planned discharge. The mean number of sessions was 2.4 (SD=1.3); those who had a planned discharge received on an average 3.7 (SD 0.5) sessions and those who dropped out received on an average 1.4 (SD 0.8) sessions. There was no significant change in daily alcohol consumption and percentage days of heavy drinking (PDHD) between baseline and follow-up in the whole cohort. The SIP score reduced significantly in the whole cohort (24.5 vs 15.0, p=0.002), and also when segregated by treatment settings, and type of treatment package received. With appropriate adaptations, our intervention warrants further research as it has the potential to bridge the significant treatment gap for alcohol dependence in low- and middle- income countries.
  • Correlations between subunits of GABAA and NMDA receptors after chronic
           alcohol treatment or withdrawal and the effect of taurine in the
           hippocampus of rats
    • Abstract: Publication date: Available online 29 August 2019Source: AlcoholAuthor(s): Alana Witt Hansen, Felipe Borges Almeida, Solange Bandiera, Rianne Remus Pulcinelli, Greice Caletti, Grasiela Agnes, Leonardo Fernandes de Paula, Natália Azuaga Nietiedt, Maurício Schüler Nin, Helena Maria Tannhauser Barros, Rosane GomezAbstractChronic use of alcohol and its withdrawal impairs the delicate balance between GABAergic and glutamatergic systems. This unbalance includes changes in GABA receptors – importantly in GABAA subtypes – and glutamate receptor – especially in NMDA subtypes. A better comprehension of the different roles of GABAAR and NMDAR subunits could be helpful to define new strategies to counteract the deleterious effects observed during alcohol withdrawal. Taurine, a sulfonated amino acid, has been proposed to attenuate alcohol withdrawal symptoms due to its neuromodulatory properties. In this study, we evaluated the correlations between GABAAR and NMDAR subunits in the hippocampus of rats chronically treated with alcohol or in alcohol withdrawal, and the effects of taurine treatment on these parameters. Male Wistar rats received alcohol (2 g/kg) or water by oral gavage (control), 2x/day, for 28 days. From day 29 to 33, withdrawal rats received water instead of alcohol and all groups were reallocated to receive 100 mg/kg taurine or saline intraperitoneally, once a day. On day 34, rats were euthanized and the hippocampus was dissected for GABAAR α1, α4, δ, and γ2 and NMDAR GluN2A and GluN2B subunits mRNA expression determination by RT qPCR. There were no differences between groups in the studied GABAAR and NMDA subunits. However, we observed a correlation of α1 and γ2 subunits induced by taurine, while in the alcohol group there was a correlation between α4 and GluN2A. In the group treated with alcohol and taurine, we observed an extra correlation, between α1 and GluN2A. After 5 days of withdrawal, a correlation observed in the control group, between δ and GluN2A was reestablished. The correlation found between subunits suggests a neuroadaptation of GABAergic and glutamatergic systems in withdrawal rats. Results from this study contribute to the elucidation of the mechanisms beyond neuroadaptations observed in alcohol use and withdrawal.
  • Disinhibited Personality, Incentives, Disincentives, and Drinking-Related
    • Abstract: Publication date: Available online 28 August 2019Source: AlcoholAuthor(s): Peter R. Finn, Lindsey Fisher, Haley Mayer, Polly Ingram, Lindy Howe, Emily AtkinsonAbstractDisinhibited personality traits, such as impulsivity (IMP), excitement seeking (ES), and low harm avoidance (HA) are thought to reflect a basic vulnerability toward alcohol use disorder (AUD), however, the specific vulnerability mechanisms associated with each trait are not well understood and there are no studies of the association between disinhibited personality and drinking-related decisions. This study investigated individual differences in drinking-related decisions associated with each trait using a task that manipulated the effects of incentives and disincentives on decisions to attend and drink at different hypothetical drinking events in a sample of 430 young adults (237 men, 193 women, mean age 21.3 years) over 60% of whom had an AUD of varying severity. The results revealed each personality domain was differentially associated with different aspects of drinking decisions. Both IMP and low HA were associated with being more likely to decide to attend party events with moderate and high goal-related responsibility disincentives. We suggest that low HA is associated with reduced sensitivity to the negative consequences of not meeting a responsibility, while IMP is associated with increased discounting of future rewards (associated with meeting a responsibility) relative to the immediate reward of attending a party event. ES was associated with being more responsive to alcohol party incentives when making decisions about attending party events and deciding to drink more at events with the highest reward potential suggesting that ES is related to a reward sensitivity decision bias. IMP appears to be associated with stronger approach that results in decisions to consume more alcohol regardless of context. The results suggest specific mechanisms by which different domains of disinhibited personality affect actual drinking-related decisions.
  • The effects of social instability stress and subsequent ethanol
           consumption in adolescence on brain and behavioural development in male
    • Abstract: Publication date: Available online 26 August 2019Source: AlcoholAuthor(s): Marina L. Marcolin, Jennet L. Baumbach, Travis E. Hodges, Cheryl M. McCormickAbstractExcessive drinking in adolescence continues to be a problem, and almost a quarter of young Canadians have reported drinking five or more in one occasion in recent surveys. The consequences of such drinking may be more pronounced when commenced in adolescence, given the ongoing brain development during this period of life. Here, we investigated the consequences of three weeks intermittent access to ethanol in mid-adolescence to early adulthood in rats and the extent to which a stress history moderated the negative consequences of ethanol access. In experiment 1, male rats that underwent adolescent social instability stress (SS; daily 1 hr isolation + return to unfamiliar cage partner every day from PND 30-45) did not differ from control (CTL) rats in intake of 10% ethanol sweetened with 0.1% saccharin (access period; PND 47-66). Ethanol drinking reduced proteins relevant for synaptic plasticity (αCaMKII, βCaMKII and PSD-95) in the dorsal hippocampus, and in CTL rats only in the prefrontal cortex (αCaMKII and PSD 95), attenuating the difference between CTL and SS rats in the water-drinking group. In experiment 2, ethanol also attenuated the difference between SS and CTL rats in a social interaction test by reducing social interaction in SS rats; CTL rats, however, had a higher intake of ethanol than did SS rats during the access period. Ethanol drinking reduced baseline and fear recall recovery concentrations of corticosterone relative to those exposed only to water, although there was no effect of either ethanol or stress history on fear conditioning. Ethanol drinking did not influence intake after 9 days of withdrawal, however, ethanol-naïve SS rats drank more than did CTL rats when given a 24-hour access in adulthood. These results reveal a complex relationship between stress history and ethanol intake in adolescence on outcomes in adulthood.
  • Impact of acute ethanol exposure on body temperatures in aged, adult and
           adolescent male rats
    • Abstract: Publication date: Available online 10 August 2019Source: AlcoholAuthor(s): Meredith R. Watson, Kimberly James, Guy Mittleman, Douglas B. MatthewsAbstractThe United States population is continuing to increase in age and data suggest that by the year 2060 the population of people over the age of 65 will more than double, providing a potentially massive strain on healthcare systems. Research demonstrates individuals 65 and older continue to consume ethanol, often at high levels. However, preclinical animal models are still being developed to understand how ethanol might interact with the aged population. The current experiments investigated differential body temperature responses in aged rats compared to adult rats and adolescent rats. Aged (19 months of age), adult (70 days of age) or adolescent (30 days of age) male Sprague Dawley rats were administered 1.0 g/kg, 2.0 g/kg or 3.0 g/kg ethanol, i.p., in a balanced Latin square design. Prior to ethanol administration, a core body temperature via an anal probe was obtained, and then repeatedly determined every 60 minutes following ethanol exposure for a total of 360 minutes. In addition, a blood sample was obtained from a tail nick 60, 180 and 300 minutes following the ethanol injection to investigate the relationship of ethanol levels and body temperature in the same animals. Aged rats had significantly greater reductions in body temperature compared to either adult or adolescent rats following both the 2.0 g/kg and 3.0 g/kg ethanol injection. Additionally, adolescent rats cleared ethanol significantly faster than aged or adult animals. These experiments suggest body temperature regulation in aged rats might be more sensitive to acute ethanol compared to adult rats or adolescent rats. Future studies are needed to identify the neurobiological effects underlying the differential sensitivity in aged rats to ethanol.
  • Functional exercise capacity in inpatients with alcohol use disorder
           versus healthy controls: a pilot study
    • Abstract: Publication date: Available online 6 August 2019Source: AlcoholAuthor(s): Davy Vancampfort, Mats Hallgren, Hannelore Vandael, Michel Probst, Philip Van Hoof, Joseph Firth, Tine Van DammeAbstractThe purpose of this study was to compare the functional exercise capacity of patients with alcohol use disorders (AUD) with an age-, gender- and body mass index (BMI)-matched healthy control group. Thirty patients (22♂, 40.4±10.5years, illness duration=9.7±9.3 years) and healthy control subjects (22♂, 40.2±10.7 years) participated. Participants performed a 6-minute walk test (6MWT) to assess their functional exercise capacity, were asked about musculoskeletal problems and dyspnea, executed a standing broad jump to assess the muscular strength and completed the International Physical Activity Questionnaire (IPAQ). Patients also filled in the Positive Affect and Negative Affect Schedule (PANAS) and Alcohol Use Disorders Identification Test (AUDIT). Our data show that patients with AUD walked a significantly shorter distance on the 6MWT (649.0±72.9 meters versus 724.4±89.0 meters, P=0.001). In patients with AUD the variance in standing broad jump score explained 43.6% of the variance in the 6MWT-score. The current study demonstrates that an impaired muscle strength is negatively associated with functional outcomes in patients with AUD. Exercise interventions should be investigated in order assess whether they can ameliorate muscle strength and daily life functioning of this vulnerable population.
  • Is burden of disease differentially linked to spirits' A systematic
           scoping review and implications for alcohol policy
    • Abstract: Publication date: Available online 29 June 2019Source: AlcoholAuthor(s): Jürgen Rehm, Omer S.M. HasanAbstractMost epidemiological research on alcohol as a risk factor is based on the assumption that outcomes are linked to pattern and level of alcohol exposure where different beverages are converted into grams of ethanol. This review examines this basic assumption, that alcohol has the same impact, independent of beverage type. We conducted a systematic search on comparative research of beverage-specific alcohol exposure and consequences. Research was divided by methodology (survey, case-control, cohort, time-series analyses, interventional research). Overall, many studies showed higher risks for spirits compared to beer or wine; however, most research was not controlled adequately for confounders such as patterns of drinking. While there is no conclusive evidence for spirits being associated with more harm, given the same pattern and level of alcohol exposure, some evidence supports for certain outcomes such as injuries and poisonings a potential excess risk for spirits consumption due to rapid ethanol intake and intoxication. Accordingly, encouraging people to opt for beverages with lower alcohol content via taxation strategies has the potential to reduce alcohol-attributable harm. This does not necessarily involve switching beverage type, but also can achieved within the same beverage category, by shifting from higher to lower concentration beverages.
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