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Showing 1 - 200 of 3175 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 8)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 28, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 90, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 33, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 376, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 235, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 25, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.383, h-index: 19)
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Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 7)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 128, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 27, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 28, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 14)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 10)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 21)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 6)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 42, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 54, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Genetics     Full-text available via subscription   (Followers: 14, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 7)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 1, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 14, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.1, h-index: 2)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 375, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 9, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 333, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 9, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 429, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 9, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 50, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 42, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 42, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 189, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 61, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 14)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 165, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)

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Journal Cover Alcohol
  [SJR: 0.922]   [H-I: 66]   [11 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0741-8329
   Published by Elsevier Homepage  [3175 journals]
  • Yawning elicited by intravenous ethanol in rhesus monkeys with experience
           self-administering cocaine and ethanol: Involvement of dopamine D3
    • Authors: Paul W. Czoty; William S. John; Amy Hauck Newman; Michael A. Nader
      Pages: 1 - 5
      Abstract: Publication date: June 2018
      Source:Alcohol, Volume 69
      Author(s): Paul W. Czoty, William S. John, Amy Hauck Newman, Michael A. Nader
      Characterization of the effects of long-term alcohol consumption on the brain would be aided by the development of behavioral assays that are relatively easy to implement in animal models of alcohol use disorders. Assessing unconditioned behaviors, such as drug-elicited yawning in models that permit long-term alcohol ingestion, may be a valuable complement to more invasive and costly procedures. The present studies investigated previous unexpected findings of ethanol-induced yawning in nonhuman primates. Subjects were adult male rhesus monkeys (n = 8), all of which had experience self-administering intravenous cocaine for several years. Four monkeys also had experience consuming 2.0 g/kg ethanol over 1 h per day, 5 days per week, for 6.8–12.0 months. All monkeys received saline or ethanol (0.25–1.0 g/kg) infused intravenously (i.v.) over 10 min, and the number of yawns elicited during the infusion was counted. A second experiment in the ethanol-experienced monkeys examined whether ethanol-induced yawning could be blocked by PG01037 (1.0, 3.0 mg/kg, i.v.), a selective antagonist at dopamine D3 receptors (D3R). Ethanol significantly and dose-dependently increased yawns in the ethanol-experienced animals, but not the ethanol-naïve animals. In the ethanol-experienced monkeys, this effect of ethanol was blocked by the D3R antagonist. The pharmacology of yawning is complex and a good deal of model development remains to be performed to characterize the potential involvement of other neurotransmitter systems. Nonetheless, drug-elicited yawning may be a useful unconditioned behavioral assay to assess the effects of long-term alcohol consumption in established nonhuman primate models.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.10.003
      Issue No: Vol. 69 (2018)
  • Proceedings of the 2017 annual meeting of the Fetal Alcohol Spectrum
           Disorders study group
    • Authors: Jeffrey R. Wozniak; Anna Y. Klintsova; Derek A. Hamilton; Sandra M. Mooney
      Pages: 7 - 14
      Abstract: Publication date: June 2018
      Source:Alcohol, Volume 69
      Author(s): Jeffrey R. Wozniak, Anna Y. Klintsova, Derek A. Hamilton, Sandra M. Mooney
      The 2017 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was titled “Prenatal alcohol exposure in the context of multiple factors affecting brain development.” The theme was reflected in the interactions between members of the Teratology Society and the FASDSG this year. The first keynote speaker, Elaine Faustman, Ph.D., was a liaison between the societies and spoke about systems biology and the multiple genetic and environmental influences on development. The second keynote speaker, Rebecca Knickmeyer, Ph.D., discussed population neuroscience and multiple influences on brain development. The conference presented updates from three government agencies and short presentations by junior and senior investigators showcasing late-breaking FASD research. The conference was capped by Dr. John Hannigan, Ph.D., the recipient of the 2017 Henry Rosett award for career-long contributions to the field.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.10.007
      Issue No: Vol. 69 (2018)
  • The contributions of Dr. Kathleen K. Sulik to fetal alcohol spectrum
           disorders research and prevention
    • Authors: Scott E. Parnell; Edward P. Riley; Kenneth R. Warren; Kathleen T. Mitchell; Michael E. Charness
      Pages: 15 - 24
      Abstract: Publication date: June 2018
      Source:Alcohol, Volume 69
      Author(s): Scott E. Parnell, Edward P. Riley, Kenneth R. Warren, Kathleen T. Mitchell, Michael E. Charness
      Dr. Kathleen Sulik (Kathy) has spent 35 years studying fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD). Beginning with her landmark 1981 Science paper describing the early gestational window when alcohol can cause the craniofacial malformations characteristic of FAS, Kathy has contributed a vast amount of research furthering our knowledge of FASD. After her seminal work that definitively demonstrated that alcohol is the causative factor in FAS, she and her lab went on to explore and define the stage-dependent effects of early gestational alcohol exposure on the face and brain in numerous different ways throughout her career. She explored and discovered numerous mechanisms of alcohol's effects on the embryo, as well as describing several genetic factors that can modify susceptibility to developmental alcohol exposure. She did not restrict her research to the face and brain; her lab described in intricate detail the effects of developmental alcohol exposure on many different organs, including the heart, ears, kidneys, and limbs. In addition to her research, and in conjunction with NIAAA and the National Organization on Fetal Alcohol Syndrome (NOFAS), Kathy developed several FASD prevention curricula that are still in use today. Finally, as part of her drive to eradicate FAS and FASD, Kathy labored tirelessly with public policy makers to change how FASD is viewed by the public, how FASD is identified in affected individuals, and how FASD is studied by researchers. While no article could fully cover Kathy's contributions to FASD research and prevention, or her other contributions to embryology and teratology, this review will attempt to illustrate some of the highlights of Kathy's remarkable career.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.10.008
      Issue No: Vol. 69 (2018)
  • Enhanced sensitivity to socially facilitating and anxiolytic effects of
           ethanol in adolescent Sprague Dawley rats following acute prenatal ethanol
    • Authors: Sandra M. Mooney; Elena I. Varlinskaya
      Pages: 25 - 32
      Abstract: Publication date: June 2018
      Source:Alcohol, Volume 69
      Author(s): Sandra M. Mooney, Elena I. Varlinskaya
      Emerging evidence suggests that deficits in social functioning and social anxiety are associated with adolescent alcohol use. Our previous research has shown that acute exposure to a high dose of ethanol on gestational day (G) 12 produces social alterations in adolescent Sprague Dawley rats. The present study assessed whether these social alterations can affect sensitivity to acute ethanol challenge during adolescence. Pregnant females were exposed intraperitoneally (i.p.) to ethanol (2.5 g/kg followed by 1.25 g/kg in 2 h) or saline on G12, and their male and female offspring were tested on postnatal day (P) 42. Rats were challenged i.p. with one of four ethanol doses (0, 0.5, 0.75, and 1.0 g/kg), and their social behavior was assessed in a modified social interaction test. Social alterations associated with prenatal ethanol exposure and indexed via decreases of social investigation, social preference, and play fighting were evident in males and females challenged with the 0 g/kg ethanol dose. Acute ethanol increased social investigation, social preference, and play fighting in animals prenatally exposed to ethanol. In contrast, rats prenatally exposed to saline, showing no social facilitation, demonstrated significant ethanol-induced (0.75 and 1.0 g/kg) decreases in social behavior. Given that late adolescents demonstrating social alterations induced by prenatal ethanol exposure become sensitive to the socially anxiolytic as well as socially facilitating effects of acute ethanol, it is possible that the attractiveness of ethanol to these adolescents may be based on its ability to alleviate anxiety under social circumstances and facilitate interactions with peers.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.11.002
      Issue No: Vol. 69 (2018)
  • Prevention of alcohol-induced DNA damage by a proprietary
           glycyrrhizin/D-mannitol product: A randomized, placebo-controlled,
           cross-over human study
    • Authors: Harsha Chigurupati; Biswajit Auddy; Manish Biyani; Shrabana Chakrabarti; Sidney J. Stohs
      Pages: 33 - 39
      Abstract: Publication date: June 2018
      Source:Alcohol, Volume 69
      Author(s): Harsha Chigurupati, Biswajit Auddy, Manish Biyani, Shrabana Chakrabarti, Sidney J. Stohs
      Objectives The purpose of the present study was to evaluate the ability of a proprietary combination of glycyrrhizin and D-mannitol to protect against oxidative damage to DNA associated with acute alcohol consumption by human subjects in a randomized, placebo-controlled cross-over designed study. Excessive alcohol consumption is associated with numerous diseases. Alcohol has been shown to generate reactive oxygen species that can result in DNA damage, leading to genetic and epigenetic changes. Methods A total of 25 subjects (13 male and 12 female) were enrolled. Alcohol intake in the form of vodka (40% ethanol) was adjusted based on 1.275 g of 100% ethanol/kg body weight for men and 1.020 g/kg body weight for women, which was consumed with and without the study product. Blood samples were drawn at 2 h after alcohol consumption, lymphocytes were isolated, and were subjected to DNA comet electrophoresis on a blinded basis. Results Acute alcohol consumption increased lymphocyte DNA damage by approximately 8.36%. Co-consumption of the glycyrrhizin/D-mannitol study product with alcohol reduced DNA damage to baseline levels. No adverse effects were associated with use of the study product, and no differences were observed in blood alcohol concentrations in the presence or absence of the study product in males and females. Conclusions Acute alcohol ingestion resulted in measurable increases in DNA damage, which were prevented by the addition of the proprietary glycyrrhizin/D-mannitol (NTX®) study product to the alcohol, suggesting that the tissue-damaging effects of alcohol consumption can be ameliorated.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.11.001
      Issue No: Vol. 69 (2018)
  • Summary of the 2017 Alcohol and Immunology Research Interest Group (AIRIG)
    • Authors: Holly J. Hulsebus; Brenda J. Curtis; Patricia E. Molina; Majid Afshar; Lisbeth A. Boule; Niya Morris; Ali Keshavarzian; Jay K. Kolls; Samantha M. Yeligar; Michael E. Price; Todd A. Wyatt; Mashkoor A. Choudhry; Elizabeth J. Kovacs
      Pages: 51 - 56
      Abstract: Publication date: June 2018
      Source:Alcohol, Volume 69
      Author(s): Holly J. Hulsebus, Brenda J. Curtis, Patricia E. Molina, Majid Afshar, Lisbeth A. Boule, Niya Morris, Ali Keshavarzian, Jay K. Kolls, Samantha M. Yeligar, Michael E. Price, Todd A. Wyatt, Mashkoor A. Choudhry, Elizabeth J. Kovacs
      On June 24, 2017, the 22nd annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite conference during the annual Research Society on Alcoholism (RSA) Scientific Meeting in Denver, Colorado. The 2017 meeting focused broadly on mechanisms that link alcohol to tissue injury and inflammation, and how this research can be translated to improve human health. Two plenary sessions composed the meeting, which first explored the association between alcohol and trauma/tissue injury, and finished with a discussion of alcohol and mucosal inflammation. The presentations encompassed diverse areas of alcohol research, from effects on the brain, to airway and pulmonary systems, to gut barrier disruption. The discussions also thoughtfully highlighted how current laboratory and clinical research can be used to prevent or treat alcohol-related morbidity and mortality.

      PubDate: 2018-04-12T01:05:11Z
      DOI: 10.1016/j.alcohol.2017.10.006
      Issue No: Vol. 69 (2018)
  • Enhanced erythrocyte antioxidant status following an 8-week aerobic
           exercise training program in heavy drinkers
    • Authors: Kalliopi Georgakouli; Eirini Manthou; Ioannis G. Fatouros; Panagiotis Georgoulias; Chariklia K. Deli; Yiannis Koutedakis; Yannis Theodorakis; Athanasios Z. Jamurtas
      Pages: 57 - 62
      Abstract: Publication date: June 2018
      Source:Alcohol, Volume 69
      Author(s): Kalliopi Georgakouli, Eirini Manthou, Ioannis G. Fatouros, Panagiotis Georgoulias, Chariklia K. Deli, Yiannis Koutedakis, Yannis Theodorakis, Athanasios Z. Jamurtas
      Alcohol-induced oxidative stress is involved in the development and progression of various pathological conditions and diseases. On the other hand, exercise training has been shown to improve redox status, thus attenuating oxidative stress-associated disease processes. The purpose of the present study was to evaluate the effect of an exercise training program that has been previously reported to decrease alcohol consumption on blood redox status in heavy drinkers. In a non-randomized within-subject design, 11 sedentary, heavily drinking men (age: 30.3 ± 3.5 years; BMI: 28.4 ± 0.86 kg/m2) participated first in a control condition for 4 weeks, and then in an intervention where they completed an 8-week supervised aerobic training program of moderate intensity (50–60% of the heart rate reserve). Blood samples were collected in the control condition (pre-, post-control) as well as before, during (week 4 of the training program), and after intervention (week 8 of the training program). Samples were analyzed for total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), uric acid (UA), bilirubin, reduced glutathione (GSH), and catalase activity. No significant change in indices of redox status in the pre- and post-control was observed. Catalase activity increased (p < 0.05) after 8 weeks of intervention compared to week 4. GSH increased (p < 0.05) after 8 weeks of intervention compared to the control condition and to week 4 of intervention. TAC, UA, bilirubin, TBARS, and PC did not significantly change at any time point. Moreover, concentrations of GSH, TBARS, and catalase activity negatively correlated with alcohol consumption. In conclusion, an 8-week aerobic training program enhanced erythrocyte antioxidant status in heavy drinkers, indicating that aerobic training may attenuate pathological processes caused by alcohol-induced oxidative stress.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.11.035
      Issue No: Vol. 69 (2018)
  • Both alcoholic and non-alcoholic steatohepatitis association with
           cardiovascular risk and liver fibrosis
    • Authors: Beatriz A. Sánchez-Jiménez; Diana Brizuela-Alcántara; Martha H. Ramos-Ostos; Luis F. Alva-López; Misael Uribe-Esquivel; Norberto C. Chávez-Tapia
      Pages: 63 - 67
      Abstract: Publication date: June 2018
      Source:Alcohol, Volume 69
      Author(s): Beatriz A. Sánchez-Jiménez, Diana Brizuela-Alcántara, Martha H. Ramos-Ostos, Luis F. Alva-López, Misael Uribe-Esquivel, Norberto C. Chávez-Tapia
      Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Mortality in NAFLD is mainly related to cardiovascular disease (CVD) and cancer. NAFLD and its association with both CVD and liver disease risk have been well evaluated, but the association of NAFLD with alcohol, known as “both alcoholic and non-alcoholic steatohepatitis” (BASH), remains uncertain. The objective of this study was to assess the influence of alcohol and obesity in the development of liver and cardiovascular disease risk. Methods This was a case-control study that included patients from a regular check-up. Alcohol consumption was evaluated with MAST, AUDIT, and CAGE. Cardiovascular risk was evaluated using the Framingham score, and liver fibrosis was evaluated with APRI and NAFLD score. Patients were classified in five groups: healthy patients, steatosis with obesity, steatosis with alcoholism, BASH, and idiopathic steatosis. Results A total of 414 patients were included. The BASH group represented 16% of patients, and showed a greater proportion of patients with high cardiovascular risk with 17% (p = 0.001), and liver fibrosis with 9%, according to the APRI score (p = 0.10). A multivariate logistic regression showed that alcohol consumption >140 g/week (OR 2.546, 95% CI 1.11–5.81, p = 0.003) and BMI >25 kg/m2 (OR 12.64, 95% CI 1.66 96.20, p = 0.001) were related to high cardiovascular risk. Liver fibrosis according to APRI was only related to alcohol consumption >140 g/week (OR 2.74, 95% CI 1–7.48, p = 0.03). Conclusions BASH remains an area not well explored, and of great implication given the increasing number of patients affected. We observed an additive effect of both etiologies in the development of high cardiovascular and liver disease risk.

      PubDate: 2018-04-16T01:18:06Z
      DOI: 10.1016/j.alcohol.2017.11.004
      Issue No: Vol. 69 (2018)
  • QTc prolongation, increased NT-proBNP and pre-clinical myocardial wall
           remodeling in excessive alcohol consumers: The SABPA study
    • Authors: Annemarie Wentzel; Leoné Malan; Jacobus D. Scheepers; Nicolaas T. Malan
      Pages: 1 - 8
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): Annemarie Wentzel, Leoné Malan, Jacobus D. Scheepers, Nicolaas T. Malan
      Alcohol contributes greatly to vascular and structural modifications. Due to differences in the metabolism and tolerance of alcohol between ethnic groups, the manner of these modifications may differ. We investigated the association between alcohol consumption – measured via ethnic-specific gamma glutamyl transferase (γ-GT) cut-points – and markers of cardiac perfusion, electrical activity, and pre-clinical structural alterations. A South African target population study was performed in a bi-ethnic cohort (n = 405). Alcohol consumption was determined according to previously defined ethnic-specific γ-GT cut-points, where γ-GT ≥ 19.5 U/L and γ-GT ≥ 55 U/L indicated excessive alcohol consumption in Caucasians and Africans, respectively. Ambulatory 24-h blood pressure and electrocardiograms (ECG), 10-lead ECG left ventricular hypertrophy (LVH), ischemic events, N-terminal pro-brain natriuretic peptide (NT-proBNP), and QTc prolongation were assessed. Fasting blood samples were obtained. A poorer cardio-metabolic profile and mean 24-h hypertensive and ECG-LVH values were evident in high γ-GT groups of both ethnicities, when compared to their low counterparts. The African high γ-GT group reported a higher intake of alcohol and presented significant increases in NT-proBNP (p < 0.001), QTc prolongation (p = 0.008), and ischemic events (p = 0.013). Regression analyses revealed associations between ECG-LVH and NT-proBNP, QTc prolongation, ischemic events, and SBP, in the African high γ-GT group exclusively. High alcohol consumers presented delayed electrical conduction in the heart accompanied by ECG-LVH, ischemic events, and increased vaso-responsiveness, predominantly in Africans. Ultimately, increased left ventricular distension on a pre-clinical level may elevate the risk for future cardiovascular events in this population.

      PubDate: 2018-02-05T10:43:57Z
      DOI: 10.1016/j.alcohol.2017.09.001
      Issue No: Vol. 68 (2018)
  • Alcohol-naïve USVs distinguish male HAD-1 from LAD-1 rat strains
    • Authors: Nitish Mittal; Neha Thakore; James M. Reno; Richard L. Bell; W. Todd Maddox; Timothy Schallert; Christine L. Duvauchelle
      Pages: 9 - 17
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): Nitish Mittal, Neha Thakore, James M. Reno, Richard L. Bell, W. Todd Maddox, Timothy Schallert, Christine L. Duvauchelle
      Ultrasonic vocalizations (USVs) are mediated through specific dopaminergic and cholinergic neural pathways and serve as real-time measures of positive and negative emotional status in rodents. Although most USV studies focus primarily on USV counts, each USV possesses a number of characteristics shown to reflect activity in the associated neurotransmitter system. In the present study, we recorded spontaneously emitted USVs from alcohol-naïve high alcohol drinking (HAD-1) and low alcohol drinking (LAD-1) rats. Using our recently developed WAAVES algorithm, we quantified four acoustic characteristics (mean frequency, duration, power, and bandwidth) from each 22–28 kHz and 50–55 kHz frequency-modulated (FM) USV. This rich USV representation allowed us to apply advanced statistical techniques to identify the USV acoustic characteristics that distinguished HAD-1 from LAD-1 rats. Linear mixed models (LMM) examined the predictability of each USV characteristic in isolation and linear discriminant analysis (LDA), and binomial logistic regression examined the predictability of linear combinations of the USV characteristics as a group. Results revealed significant differences in acoustic characteristics between HAD-1 and LAD-1 rats in both 22–28 kHz and 50–55 kHz FM USVs. In other words, these rats selectively bred for high- and low-alcohol consumption can be identified as HAD-1 or LAD-1 rats with high classification accuracy (approximately 92–100%) exclusively based on their emitted 22–28 kHz and 50–55 kHz FM USV acoustic characteristics. In addition, acoustic characteristics of 22–28 kHz and 50–55 kHz FM USVs emitted by alcohol-naïve HAD-1 and LAD-1 rats significantly correlate with their future alcohol consumption. Our current findings provide novel evidence that USV acoustic characteristics can be used to discriminate between alcohol-naïve HAD-1 and LAD-1 rats, and may serve as biomarkers in rodents with a predisposition for, or against, excessive alcohol intake.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.09.003
      Issue No: Vol. 68 (2018)
  • An alcohol withdrawal test battery measuring multiple behavioral symptoms
           in mice
    • Authors: Pamela Metten; Jason P. Schlumbohm; Lawrence C. Huang; Gian D. Greenberg; Wyatt R. Hack; Stephanie E. Spence; John C. Crabbe
      Pages: 19 - 35
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): Pamela Metten, Jason P. Schlumbohm, Lawrence C. Huang, Gian D. Greenberg, Wyatt R. Hack, Stephanie E. Spence, John C. Crabbe
      Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.08.014
      Issue No: Vol. 68 (2018)
  • Gene expression changes in the ventral hippocampus and medial prefrontal
           cortex of adolescent alcohol-preferring (P) rats following binge-like
           alcohol drinking
    • Authors: Jeanette N. McClintick; William J. McBride; Richard L. Bell; Zheng-Ming Ding; Yunlong Liu; Xiaoling Xuei; Howard J. Edenberg
      Pages: 37 - 47
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): Jeanette N. McClintick, William J. McBride, Richard L. Bell, Zheng-Ming Ding, Yunlong Liu, Xiaoling Xuei, Howard J. Edenberg
      Binge drinking of alcohol during adolescence is a serious public health concern with long-term consequences, including decreased hippocampal and prefrontal cortex volume and deficits in memory. We used RNA sequencing to assess the effects of adolescent binge drinking on gene expression in these regions. Male adolescent alcohol-preferring (P) rats were exposed to repeated binge drinking (three 1-h sessions/day during the dark/cycle, 5 days/week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5–3 g/kg/session). Ethanol significantly altered the expression of 416 of 11,727 genes expressed in the ventral hippocampus. Genes and pathways involved in neurogenesis, long-term potentiation, and axonal guidance were decreased, which could relate to the impaired memory function found in subjects with adolescent alcohol binge-like exposure. The decreased expression of myelin and cholesterol genes and apparent decrease in oligodendrocytes in P rats could result in decreased myelination. In the medial prefrontal cortex, 638 of 11,579 genes were altered; genes in cellular stress and inflammatory pathways were increased, as were genes involved in oxidative phosphorylation. Overall, the results of this study suggest that adolescent binge-like alcohol drinking may alter the development of the ventral hippocampus and medial prefrontal cortex and produce long-term consequences on learning and memory, and on control of impulsive behaviors.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.09.002
      Issue No: Vol. 68 (2018)
  • Implications of altered maternal cytokine concentrations on infant
           outcomes in children with prenatal alcohol exposure
    • Authors: K.D. Sowell; J.Y. Uriu-Adams; J. Van de Water; C.D. Chambers; C.D. Coles; J.A. Kable; L. Yevtushok; N. Zymak-Zakutnya; W. Wertelecki; C.L. Keen
      Pages: 49 - 58
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): K.D. Sowell, J.Y. Uriu-Adams, J. Van de Water, C.D. Chambers, C.D. Coles, J.A. Kable, L. Yevtushok, N. Zymak-Zakutnya, W. Wertelecki, C.L. Keen
      Excessive alcohol consumption has been shown to increase serum plasma levels of numerous immune cytokines. Maternal immune activation and elevated cytokines have been implicated in certain neurological disorders (e.g., autism and schizophrenia) in the offspring. We investigated the hypothesis that elevated cytokines during pregnancy are a risk factor in women who gave birth to a child with Fetal Alcohol Spectrum Disorder (FASD) or a child with neurobehavioral impairment, regardless of prenatal alcohol exposure. Moderate to heavy alcohol-exposed (AE) (N = 149) and low or no alcohol-exposed (LNA) (N = 92) women were recruited into the study during mid pregnancy (mean of 19.8 ± 5.8 weeks' gestation) in two regions of Ukraine: Khmelnytsky and Rivne. Maternal blood samples were obtained at enrollment into the study at early to mid-pregnancy and during a third-trimester follow-up visit and analyzed for plasma cytokines. Children were examined at 6 and/or 12 months of age and were classified as having FASD if their mothers reported alcohol use and if they had at least one standardized score (Bayley Scales of Infant Development II Mental Development Index [MDI], or Psychomotor Development Index [PDI]) below 85 with the presence or absence of physical features of FASD. In multivariate analyses of maternal cytokine levels in relation to infant MDI and PDI scores in the entire sample, increases in the ratio of TNF-α/IL-10 and IL-6/IL-10 were negatively associated with PDI scores at 6 months (p = 0.020 and p = 0.036, respectively) and 12 months (p = 0.043 and p = 0.029, respectively), and with MDI scores at 12 months (p = 0.013 and p = 0.050, respectively). A reduction in the odds ratio of having an FASD child was observed with increasing levels of IL-1β, IL-2, IL-4, IL-6, and IL-10 in early to mid-pregnancy and IL-1β and IL-10 during late pregnancy. However, women that failed to increase IL-10 levels in the third trimester in order to maintain the balance of pro- and anti-inflammatory cytokines had an elevated risk of having an FASD child, specifically a significant increase in the odds ratio of FASD with every one-unit log increase in late pregnancy TNF-α/IL-10 levels (aOR: 1.654, CI: 1.096–2.495, p = 0.017). These data support the concept that disruptions in the balance between pro- and anti-inflammatory cytokines may contribute to neurobehavioral impairment and alter the risk of FASD.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.08.006
      Issue No: Vol. 68 (2018)
  • Association between alcoholism and the gene encoding the endocannabinoid
           synthesizing enzyme diacylglycerol lipase alpha in the Japanese population
    • Authors: Hiroki Ishiguro; Susumu Higuchi; Tadao Arinami; Emmanuel S. Onaivi
      Pages: 59 - 62
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): Hiroki Ishiguro, Susumu Higuchi, Tadao Arinami, Emmanuel S. Onaivi
      The endocannabinoid system has been recognized to be involved in neuropsychiatric diseases. 2-arachidonoyl glycerol (2-AG) is one of the two main endocannabinoids, and their regulation could play roles in disorders under environmental influence. This study investigated the involvement of the 2-AG biosynthesizing enzyme diacylglycerol lipase alpha (DAGLA) in the pathogenesis of alcoholism. We investigated a possible association between alcoholism and single nucleotide polymorphisms (SNPs) of the human DAGLA gene in the Japanese population. To discern any environmental influences on Dagla function in an animal study, the Dagla gene expression in the brain from stressed model mice was analyzed. The SNPs, including missense polymorphism Pro899Leu in the DAGLA gene, showed associations with alcoholism in the Japanese population. Dagla expression in mice was found to be influenced by chronic mild stress and by the acquisition of alcohol preference. Our findings indicated the involvement of DAGLA in alcoholism, possibly by its genetic dysfunction and also by the influence of stress.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.09.005
      Issue No: Vol. 68 (2018)
  • Reduced expression of purinergic P2X4 receptors increases voluntary
           ethanol intake in C57BL/6J mice
    • Authors: Sheraz Khoja; Nhat Huynh; Liana Asatryan; Michael W. Jakowec; Daryl L. Davies
      Pages: 63 - 70
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): Sheraz Khoja, Nhat Huynh, Liana Asatryan, Michael W. Jakowec, Daryl L. Davies
      Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ionotropic receptors that are gated by adenosine 5′-triphosphate (ATP). Accumulating evidence indicates that P2X4Rs play an important role in regulation of ethanol intake. At the molecular level, ethanol's inhibitory effects on P2X4Rs are antagonized by ivermectin (IVM), in part, via action on P2X4Rs. Behaviorally, male mice deficient in the p2rx4 gene (P2X4R knockout [KO]) have been shown to exhibit a transient increase in ethanol intake over a period of 4 days, as demonstrated by social and binge drinking paradigms. Furthermore, IVM reduced ethanol consumption in male and female rodents, whereas male P2X4R KO mice were less sensitive to the anti-alcohol effects of IVM, compared to wildtype (WT) mice, further supporting a role for P2X4Rs as targets of IVM's action. The current investigation extends testing the hypothesis that P2X4Rs play a role in regulation of ethanol intake. First, we tested the response of P2X4R KO mice to ethanol for a period of 5 weeks. Second, to gain insights into the changes in ethanol intake, we employed a lentivirus-shRNA (LV-shRNA) methodology to selectively knockdown P2X4R expression in the nucleus accumbens (NAc) core in male C57BL/6J mice. In agreement with our previous study, male P2X4R KO mice exhibited higher ethanol intake than WT mice. Additionally, reduced expression of P2X4Rs in the NAc core significantly increased ethanol intake and preference. Collectively, the findings support the hypothesis that P2X4Rs play a role in regulation of ethanol intake and that P2X4Rs represent a novel drug target for treatment of alcohol use disorder.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.09.004
      Issue No: Vol. 68 (2018)
  • Involvement of neuronal nitric oxide synthase in cross-sensitization
           between chronic unpredictable stress and ethanol in adolescent and adult
    • Authors: Jaqueline Borges Santos-Rocha; Mariana Rae; Ana Maria Aristimunho Teixeira; Simone Aparecida Teixeira; Carolina Demarchi Munhoz; Marcelo Nicolas Muscará; Tania Marcourakis; Karen K. Szumlinski; Rosana Camarini
      Pages: 71 - 79
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): Jaqueline Borges Santos-Rocha, Mariana Rae, Ana Maria Aristimunho Teixeira, Simone Aparecida Teixeira, Carolina Demarchi Munhoz, Marcelo Nicolas Muscará, Tania Marcourakis, Karen K. Szumlinski, Rosana Camarini
      The peculiar neurochemical profile of the adolescent brain renders it differently susceptible to several stimuli, including stress and/or drug exposure. Among several stress mediators, nitric oxide (NO) has a role in stress responses. We have demonstrated that adolescent mice are less sensitive to ethanol-induced sensitization than adult mice. The present study investigated whether chronic unpredictable stress (CUS) induces behavioral sensitization to ethanol in adolescent and adult Swiss mice, and investigated the influence of Ca2+-dependent nitric oxide synthase (NOS) activity in the phenomenon. Adolescent and adult mice were exposed to repeated 1.8 g/kg ethanol or CUS and challenged with saline or ethanol. A neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7NI), was administered along with ethanol and CUS to test its effects on behavioral sensitization. Both adolescent and adult mice displayed cross-sensitization between CUS and ethanol in adult mice, with adolescents showing a lower degree of sensitization than adults. nNOS inhibition by 7NI reduced both ethanol sensitization and cross-sensitization. All age differences in the Ca2+-dependent NOS activity in the hippocampus and prefrontal cortex were in the direction of greater activity in adults than in adolescents. Adolescents showed lower sensitivity to cross-sensitization between CUS and ethanol, and the nitric oxide (NO) system seems to have a pivotal role in ethanol-induced behavioral sensitization and cross-sensitization in both adolescent and adult mice.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.10.004
      Issue No: Vol. 68 (2018)
  • Borderline personality disorder symptoms in treatment-naïve actively
           drinking alcoholics
    • Authors: George Fein; Mathew Price; Valerie A. Cardenas
      Pages: 81 - 89
      Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68
      Author(s): George Fein, Mathew Price, Valerie A. Cardenas
      Borderline personality disorder (BPD) is often a complicating comorbid factor in alcohol use disorders and substance use disorders. Previous work showed that abstinent alcoholics endorsed lifetime and current symptoms of most of the BPD criteria at much higher rates than controls, with much higher symptom counts for short-term abstinent alcoholic (STAA) women than men, which is consistent with such symptoms negatively affecting female alcoholics' ability to maintain abstinence. Because prior work has also shown that treatment-naïve alcoholics (TNA) are not the same as treated alcoholics observed earlier in their alcohol dependence, but rather are a different population with potentially lower psychiatric comorbidity, in this study we compared BPD symptom criteria between TNA samples of comparable age to the control and STAA samples, including both men and women and individuals dependent on alcohol only or with lifetime dependence on both alcohol and drugs. BPD symptoms were obtained using the SCID-II, and endorsed symptoms were classified as current or lifetime. Logistic regression analyses were used to test for effects of group, sex, presence of a lifetime drug dependence diagnosis, and their interactions for lifetime and current symptom endorsement for each BPD criteria. Groups were compared pairwise (TNA vs. NSAC, and STAA vs. TNA). The effect of a lifetime drug dependence diagnosis was not significant for any BPD symptom variable, consistent with the alcohol groups’ BPD symptoms being unaffected by the presence of a comorbid drug dependence. The primary result presented here is that TNA women have borderline symptomatology more similar to that of treated STAA than to NSAC, while TNA men have borderline symptomatology more similar to NSAC than to STAA. A visual examination of co-occurring BPD symptoms showed that while more BPD symptoms are likely to be present in TNA and STAA vs. NSAC, there is no grouping of criteria (i.e., symptom cluster) that is characteristic of TNA or STAA.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2017.10.005
      Issue No: Vol. 68 (2018)
  • Maternal hair testing to disclose self-misreporting in drinking and
           smoking behavior during pregnancy
    • Authors: Maria Dolores Gomez-Roig; Emilia Marchei; Sally Sabra; Francesco Paolo Busardò; Luisa Mastrobattista; Simona Pichini; Eduard Gratacós; Oscar Garcia-Algar
      Pages: 1 - 6
      Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67
      Author(s): Maria Dolores Gomez-Roig, Emilia Marchei, Sally Sabra, Francesco Paolo Busardò, Luisa Mastrobattista, Simona Pichini, Eduard Gratacós, Oscar Garcia-Algar
      This study aimed to objectively verify smoking and drinking behavior during pregnancy and to disclose self-misreporting through maternal hair analysis. A total of 153 women attending a university hospital in Barcelona (Spain) were selected and interviewed after delivery, on their smoking and drinking habits during pregnancy. A 9-cm hair strand was collected and analyzed by liquid chromatography tandem mass spectrometry for the presence of nicotine (NIC) and ethyl glucuronide (EtG) as biomarkers of tobacco and alcohol consumption, respectively. Concentrations of EtG <7 pg/mg hair and ≥30 pg/mg hair in the 0–3-cm hair segment have been used to assess, respectively, total abstinence and chronic excessive consumption in the previous 3 months, with repetitive moderate drinking lying in the interval 7–30 pg EtG per mg hair. Hair NIC less than 1 ng/mg hair indicates non-exposure to tobacco smoke while hair NIC indicates daily active smoking. In the interview, 28.1% of women declared to have smoked occasionally during gestation, while only 2.6% stated to have consumed alcohol on more than one occasion during pregnancy. Hair testing of smoking biomarkers disclosed that 7.2% of women remained active smokers during the whole pregnancy (hair NIC: 3.21–56.98 ng/mg hair), 16.3% were passive non-smokers or occasional smokers (hair NIC: 1.04–2.99 ng/mg hair), while 76.5% were not exposed to any cigarette smoke (hair NIC < limit of quantification – 0.91 ng/mg hair). Conversely, alcohol hair biomarkers showed that only 35.3% of women were totally abstinent during gestation (hair EtG: 3.89–6.73 pg/mg hair), while 62.7% drank a non-negligible amount of alcohol during pregnancy (hair EtG: 7.06–26.57 pg/mg hair), and 2% were chronic excessive drinkers (hair EtG: 35.33–47.52 pg/mg hair). Maternal hair analysis has shown to be significantly more sensitive than interviews in revealing an alarming misreported prevalence of alcohol use during pregnancy. These findings stress the need to use objective measures to assess alcohol exposure and to consider the inclusion of targeted actions to reduce alcohol consumption in maternal-child health policies.

      PubDate: 2018-02-05T10:43:57Z
      DOI: 10.1016/j.alcohol.2017.08.010
      Issue No: Vol. 67 (2018)
  • Evaluation of a novel method for the analysis of alcohol biomarkers: Ethyl
           glucuronide, ethyl sulfate and phosphatidylethanol
    • Authors: Van Long Nguyen; Phillip Paull; Paul S. Haber; Kate Chitty; Devanshi Seth
      Pages: 7 - 13
      Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67
      Author(s): Van Long Nguyen, Phillip Paull, Paul S. Haber, Kate Chitty, Devanshi Seth
      Currently available markers and methods to evaluate alcohol consumption are indirect and suboptimal, or rely on self-report, which have inherent problems. Direct metabolites of alcohol, phosphatidylethanol (PEth), ethyl sulfate (EtS), and ethyl glucuronide (EtG), are known to improve diagnostic accuracy. In this study, methods were established for the identification of PEth in erythrocytes and EtG and EtS in serum using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The three biomarkers were tested and validated in volunteer teetotalers (n = 4) and drinkers (n = 10), and applied in patients (n = 8) hospitalized with alcohol-related problems. Linearity of each assay was demonstrated from 22.5 to 900 nM for EtG, 40–3175 nM for EtS, and 21–750 nM for PEth. The methods were highly selective, precise (<5% coefficient of variation), and had optimal accuracy (within 10% of the nominal value) for all three analytes. Recovery for all three compounds exceeded 90%. A preliminary investigation into the window of detection of these biomarkers after a single occasion of moderate alcohol consumption revealed that EtG and EtS could be detected and quantified over the short term (days) and PEth over the long term (weeks). All three biomarkers showed high sensitivity and specificity in distinguishing between abstinence and any alcohol use at the cut-off values of 22.5 nM for EtG, 40 nM for EtS, and 21 nM for PEth. We have established simultaneous assays for EtG, EtS, and PEth for routine clinical use in confirming abstinence and exposure, and detecting under-reporting of alcohol use, relevant in clinical and non-clinical settings.

      PubDate: 2018-02-05T10:43:57Z
      DOI: 10.1016/j.alcohol.2017.08.009
      Issue No: Vol. 67 (2018)
  • Differential COMT expression and behavioral effects of COMT inhibition in
           male and female Wistar and alcohol preferring rats
    • Authors: Aqilah M. McCane; Michael J. DeLory; Maureen M. Timm; Sarine S. Janetsian-Fritz; Christopher C. Lapish; Cristine L. Czachowski
      Pages: 15 - 22
      Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67
      Author(s): Aqilah M. McCane, Michael J. DeLory, Maureen M. Timm, Sarine S. Janetsian-Fritz, Christopher C. Lapish, Cristine L. Czachowski
      Polymorphisms of the catechol-O-methyl transferase (COMT) gene have been associated with alcoholism, suggesting that alterations in the metabolism of catecholamines may be a critical component of the neuropathology of alcoholism. In the current experiments, the COMT inhibitor tolcapone was utilized in an operant behavioral model of reinforcer-seeking and drinking to determine if this compound was capable of remediating the excessive seeking and drinking phenotype of the alcohol-preferring P rat. Tolcapone was administered to male and female alcohol-reinforced P and Wistar rats. Additionally, tolcapone was administered to male sucrose-reinforced P and Wistar rats to determine if its effects also extended to a natural reinforcer. Animals were trained to make an operant response that resulted in 20 min uninterrupted access to the reinforcer solutions. Tolcapone had no effect in female rats on either seeking or consumption of ethanol. However, reductions of both reinforcer seeking and consumption were observed in male P rats, but only of seeking in Wistars. In separate experiments, using reinforcer naïve male and female animals, COMT expression was assessed via Western Blot analysis. Sex differences in COMT expression were also observed, where male P rats exhibited a marked reduction in protein expression relative to females in the PFC. Sex differences were not observed for Wistars or in the striatum and hippocampus. These data complement our previous findings in which tolcapone reduced cue-evoked responses in P rats and further suggest clinical utility of COMT inhibitors in the treatment of addiction disorders, specifically in male high drinkers.

      PubDate: 2018-02-05T10:43:57Z
      DOI: 10.1016/j.alcohol.2017.08.007
      Issue No: Vol. 67 (2018)
  • Alcohol operant self-administration: Investigating how alcohol-seeking
           behaviors predict drinking in mice using two operant approaches
    • Authors: Mariah B. Blegen; Daniel da Silva E Silva; Roland Bock; Nadege Morisot; Dorit Ron; Veronica A. Alvarez
      Pages: 23 - 36
      Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67
      Author(s): Mariah B. Blegen, Daniel da Silva E Silva, Roland Bock, Nadege Morisot, Dorit Ron, Veronica A. Alvarez
      Alcohol operant self-administration paradigms are critical tools for studying the neural circuits implicated in both alcohol-seeking and consummatory behaviors and for understanding the neural basis underlying alcohol-use disorders. In this study, we investigate the predictive value of two operant models of oral alcohol self-administration in mice, one in which alcohol is delivered into a cup following nose-poke responses with no accurate measurement of consumed alcohol solution, and another paradigm that provides access to alcohol via a sipper tube following lever presses and where lick rate and consumed alcohol volume can be measured. The goal was to identify a paradigm where operant behaviors such as lever presses and nose pokes, as well as other tracked behavior such as licks and head entries, can be used to reliably predict blood alcohol concentration (BAC). All mice were first exposed to alcohol in the home cage using the “drinking in the dark” (DID) procedure for 3 weeks and then were trained in alcohol self-administration using either of the operant paradigms for several weeks. Even without sucrose fading or food pre-training, mice acquired alcohol self-administration with both paradigms. However, neither lever press nor nose-poke rates were good predictors of alcohol intake or BAC. Only the lick rate and consumed alcohol were consistently and significantly correlated with BAC. Using this paradigm that accurately measures alcohol intake, unsupervised cluster analysis revealed three groups of mice: high-drinking (43%), low-drinking (37%), and non-drinking mice (20%). High-drinking mice showed faster acquisition of operant responding and achieved higher BACs than low-drinking mice. Lick rate and volume consumed varied with the alcohol concentration made available only for high- and low-drinking mice, but not for non-drinking mice. In addition, high- and low-drinking mice showed similar patterns during extinction and significant cue-induced reinstatement of seeking. Only high-drinking mice showed insensitivity to quinine adulteration, indicating a willingness to drink alcohol despite pairing with aversive stimuli. Thus, this study shows that relying on active presses is not an accurate determination of drinking behavior in mice. Only paradigms that allow for accurate measurements of consumed alcohol and/or lick rate are valid models of operant alcohol self-administration, where compulsive-like drinking could be accurately determined based on changes in alcohol intake when paired with bitter-tasting stimuli.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.08.008
      Issue No: Vol. 67 (2018)
  • Challenges of diagnosing fetal alcohol spectrum disorders in foster and
           adopted children
    • Authors: Ludmila N. Bakhireva; Laura Garrison; Shikhar Shrestha; Janet Sharkis; Rajesh Miranda; Karen Rogers
      Pages: 37 - 43
      Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67
      Author(s): Ludmila N. Bakhireva, Laura Garrison, Shikhar Shrestha, Janet Sharkis, Rajesh Miranda, Karen Rogers
      Fetal Alcohol Spectrum Disorders (FASD) might be 10–15 times more prevalent among foster/adopted children compared to the general population; however, many of these children remain undiagnosed or misdiagnosed. The lack of confirmed prenatal alcohol exposure (PAE) may be a key barrier to diagnosis. Our sample included 681 patients evaluated for FASD, according to the University of Washington 4-Digit Diagnostic Code, at a pediatric specialty clinic. Guardianship status and other patient characteristics were evaluated by multinomial logistic regression as potential predictors of being classified into one of the following FASD groups: 1) full or partial Fetal Alcohol Syndrome (FAS/pFAS; n = 97); 2) Static Encephalopathy/Alcohol-Exposed (SE/AE) or Neurobehavioral Disorder/Alcohol-Exposed (ND/AE) (n = 135); and 3) some features of FASD (equivalent to pFAS, SE/AE or ND/AE phenotypes) but unknown PAE (n = 449). Median age at assessment was 7.0 years, non-Hispanic White constituted the predominant racial/ethnic group (49.5%), and the majority (81.8%) lacked involvement from a biological parent/relative. Many patients (66.0%) had some features of FASD but lacked reliable PAE information. Children classified into the ‘some features/unknown PAE’ group had higher median age of assessment (8 years) compared to other groups (6 years; p < 0.001). No association was observed between race/ethnicity or child's sex and FASD outcomes (p > 0.05). Adopted/foster children were 2.8 times as likely (95% CI: 1.6; 4.8) to be classified into the ‘some features/unknown PAE’ group compared to children living with a parent/relative after adjusting for covariates. This study's findings indicate that adopted/foster children are more likely to have unknown PAE and not receive a FASD diagnosis, potentially denying them access to specialized services, treatment, and rehabilitation.

      PubDate: 2018-02-05T10:43:57Z
      DOI: 10.1016/j.alcohol.2017.05.004
      Issue No: Vol. 67 (2018)
  • Difference in sensitivities of blood HDL cholesterol and LDL cholesterol
           levels to alcohol in middle-aged Japanese men
    • Authors: Ichiro Wakabayashi
      Pages: 45 - 50
      Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67
      Author(s): Ichiro Wakabayashi
      Blood HDL cholesterol and LDL cholesterol levels are known to be higher and lower, respectively, in drinkers than in nondrinkers, and the beneficial effects of alcohol on cholesterol metabolism are thought to mainly explain the lower risk for ischemic heart disease in light-to-moderate drinkers than in nondrinkers. However, it remains unknown whether sensitivities of HDL and LDL cholesterol levels to alcohol are different or not. The subjects of this study were 21,572 middle-aged Japanese men, and they were divided into three tertile groups for blood HDL cholesterol levels. The relationships between habitual alcohol intake and LDL cholesterol levels were investigated in each tertile for HDL cholesterol. In all of the tertile groups for HDL cholesterol, mean LDL cholesterol levels were significantly lower in the drinking subgroups than in the nondrinking subgroup and tended to be lower with an increase of alcohol intake. In all of the tertile groups for HDL cholesterol, odds ratios for high LDL cholesterol of each drinking subgroup vs. the nondrinking subgroup were significantly lower than the reference level of 1.00, and also tended to be lower with an increase of alcohol intake. The odds ratios of each drinking subgroup tended to be lower in the 1st tertile group for HDL cholesterol than in the 3rd tertile group. Drinkers in the 1st tertile for HDL cholesterol are thought to have relatively low sensitivity of HDL cholesterol to alcohol, but clearly showed lower LDL cholesterol levels than those found in nondrinkers. Therefore, the sensitivity of LDL cholesterol level to alcohol is different from the sensitivity of HDL cholesterol level to alcohol.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.08.011
      Issue No: Vol. 67 (2018)
  • Imaging mass spectrometry of frontal white matter lipid changes in human
    • Authors: Suzanne M. de la Monte; Jared Kay; Emine B. Yalcin; Jillian J. Kril; Donna Sheedy; Greg T. Sutherland
      Pages: 51 - 63
      Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67
      Author(s): Suzanne M. de la Monte, Jared Kay, Emine B. Yalcin, Jillian J. Kril, Donna Sheedy, Greg T. Sutherland
      Background Chronic alcohol use disorders (AUD) are associated with white matter (WM) degeneration with altered myelin integrity. Matrix assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS) enables high throughput analysis of myelin lipid biochemical histopathology to help characterize disease mechanisms. Purpose This study utilized MALDI-IMS to investigate frontal lobe WM myelin lipid abnormalities in AUD. Methods Standardized cores of formalin-fixed WM from Brodmann Area 4 (BA4) and BA8/9 of 20 postmortem AUD and 19 control adult human brains were embedded in carboxymethyl-cellulose, cryo-sectioned (8 μm), thaw-mounted onto indium tin oxide (ITO) -coated glass slides, and sublimed with 2,5-dihydroxybenzxoic acid (DHB) matrix. Lipids were imaged by MALDI-time of flight in the negative ionization mode. Data were visualized with FlexImaging software v4.0 and analyzed with ClinProTools v3.0. Results Principal component analysis (PCA) and data bar plots of MALDI-IMS data differentiated AUD from control WM. The dominant effect of AUD was to broadly reduce expression of sphingolipids (sulfatides and ceramides) and phospholipids. Data bar plots demonstrated overall similar responses to AUD in BA4 and BA8/9. However, differential regional effects of AUD on WM lipid profiles were manifested by non-overlapping expression or discordant responses to AUD for a subset of lipid ions. Conclusions Human AUD is associated with substantial inhibition of frontal lobe WM lipid expression with regional variability in these effects. MALDI-IMS can be used to characterize the nature of AUD-associated lipid biochemical abnormalities for correlation with lifetime exposures and WM degeneration, altered gene expression, and responses to abstinence or treatment.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.08.004
      Issue No: Vol. 67 (2018)
  • Persistent light to moderate alcohol intake and lung function:
           A longitudinal study
    • Authors: Monica M. Vasquez; Duane L. Sherrill; Tricia D. LeVan; Wayne J. Morgan; Joseph H. Sisson; Stefano Guerra
      Pages: 65 - 71
      Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67
      Author(s): Monica M. Vasquez, Duane L. Sherrill, Tricia D. LeVan, Wayne J. Morgan, Joseph H. Sisson, Stefano Guerra
      Alcohol intake has been inconsistently associated with lung function levels in cross-sectional studies. The goal of our study was to determine whether longitudinally assessed light-to-moderate alcohol intake is associated with levels and decline of lung function. We examined data from 1333 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease. Alcohol intake was assessed with four surveys between 1972 and 1992. Subjects who completed at least two surveys were classified into longitudinal drinking categories (“never”, “inconsistent”, or “persistent drinker”). Spirometric lung function was measured in up to 11 surveys between 1972 and 1992. Random coefficient models were used to test for differences in lung function by drinking categories. After adjustment for sex, age, height, education, BMI categories, smoking status, and pack-years, as compared to never-drinkers, persistent drinkers had higher FVC (coefficient: 157 mL, p < 0.001), but lower FEV1/FVC ratio (−2.3%, p < 0.001). Differences were due to a slower decline of FVC among persistent than among never-drinkers (p = 0.003), and these trends were present independent of smoking status. Inconsistent drinking showed similar, but weaker associations. After adjustment for potential confounders, light-to-moderate alcohol consumption was associated with a significantly decreased rate of FVC decline over adult life.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2017.08.013
      Issue No: Vol. 67 (2018)
  • Instructions to Authors
    • Abstract: Publication date: May 2018
      Source:Alcohol, Volume 68

      PubDate: 2018-04-11T01:05:04Z
  • Using human stem cells as a model system to understand the neural
           mechanisms of alcohol use disorders: current status and outlooks
    • Authors: Matthew S. Scarnati; Apoorva Halikere; Zhiping P. Pang
      Abstract: Publication date: Available online 31 March 2018
      Author(s): Matthew S. Scarnati, Apoorva Halikere, Zhiping P. Pang
      Alcohol use disorders (AUDs), which include alcohol abuse and dependence, are among the most common types of neuropsychiatric disorders in the United States. Approximately 14% of the U.S. population is affected in a single year, thus placing a tremendous strain on individuals from all socioeconomic backgrounds. Animal models have been pivotal in revealing the basic mechanisms of how alcohol impacts neuronal function; however there are currently limited effective therapies developed based on these research. This is mainly due to a limited understanding of the exact cellular and molecular mechanisms underlying AUDs in humans, which leads to a lack of targeted therapeutics. Furthermore, compounding factors including genetic background, copy number variants, single nucleotide polymorphisms (SNP) as well as environmental and social factors that affect and promote the development of AUDs are complex and heterogeneous. The recent advent in stem cell biology, especially the human induced pluripotent stem (iPS) cell development and differentiation technologies, has provided us a unique opportunity to model neuropsychiatric disorders like AUDs in a manner that is highly complementary to animal studies, but that maintains fidelity with complex human genetic contexts. Patient-specific neurons can then be used for drug discovery and precision medicine. Here, we review recent work employing iPS cell technology to model and elucidate the genetic, molecular and cellular mechanisms of AUDs in a human neuronal context and provide our perspective on future development in this direction.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.008
  • Use of alcohol biomarkers to identify alcohol misuse in organ donors
    • Authors: Erin M. Lowery; Martin Walsh; Meagan Yong; Elizabeth J. Kovacs; Cara Joyce; Majid Afshar
      Abstract: Publication date: Available online 31 March 2018
      Author(s): Erin M. Lowery, Martin Walsh, Meagan Yong, Elizabeth J. Kovacs, Cara Joyce, Majid Afshar
      Phosphatidylethanol is a direct alcohol biomarker for identifying alcohol misuse. It carries several advantages over other alcohol biomarkers including a detection half-life of several weeks and little confounding by patient characteristics or organ dysfunction. The aim of this study is to derive an optimal phosphatidylethanol cutpoint to identify organ donors with alcohol misuse, and to assess the impact of alcohol misuse on organ allocation. Discrimination of phosphatidylethanol was evaluated using the area under the ROC curve from a mixed effects logistic regression model. Phosphatidylethanol had an area under the ROC curve of 0.89 (95% CI 0.80-0.98). A phosphatidylethanol cutpoint of ≥84 ng/mL provided optimal discrimination for the identification of alcohol misuse with a sensitivity of 75% (95% CI 52.9%-89.4%) and a specificity of 97% (95% CI 91%-99%), a positive predictive value of 82% (95% CI 59%-94%), and a negative predictive value of 95% (95% CI 89%-98%). In critically ill deceased organ donors phosphatidylethanol had good test characteristics to discriminate alcohol misuse. Other alcohol biomarkers performed poorly in deceased organ donors. Liver allocation was decreased in donors with alcohol misuse by proxy history, but not in those with phosphatidylethanol >84 ng/ml, revealing possible information bias in liver allocation.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.010
  • The Center of the Emotional Universe: alcohol, stress, and CRF1 amygdala
    • Authors: Abigail Agoglia; Melissa Herman
      Abstract: Publication date: Available online 30 March 2018
      Author(s): Abigail Agoglia, Melissa Herman

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.009
  • Decreased Glucose-6-Phosphate Dehydrogenase Activity along with Oxidative
           Stress affects visual Contrast Sensitivity in Alcoholics
    • Authors: Subhasish Pramanik; Upasana Ganguly; Vineet Kumar Khemka; Anindita Banerjee
      Abstract: Publication date: Available online 21 March 2018
      Author(s): Subhasish Pramanik, Upasana Ganguly, Vineet Kumar Khemka, Anindita Banerjee
      Objective To evaluate oxidative stress and Glucose-6-phosphate dehydrogenase (G6PD) status of alcoholics and find out their association, if any, with visual contrast sensitivity function. Methods: Forty male alcoholic subjects and 36 non alcoholic subjects with same age and nutritional status were enrolled in this study. Serum malondialdehyde (MDA) level and Glucose-6-phosphate dehydrogenase (G6PD) activity of erythrocytes were determined by spectrophotometric assay. Contrast Sensitivity (CS) function of study subjects was measured using ‘Rabin Contrast Sensitivity Test’ (Precision Vision®, La Salle, IL, USA). Results: Serum MDA level was significantly higher (p< 0.0001) and erythrocytes G6PD activity was significantly lower (p= 0.0026) in alcoholic subjects compared to the controls. CS score of both eyes was also found to be decreased significantly in alcoholic subjects (both at p< 0.0001) than control subjects. On the other hand CS score of the alcoholic subjects was inversely correlated with serum MDA level (r= -0.746, p< 0.0001) and directly correlated with erythrocytes G6PD activity (r= 0.78, p< 0.0001). A strong inverse correlation (r= - 0.84, p< 0.0001) was also observed between serum MDA level and erythrocytes G6PD activity of alcoholic subjects. Conclusion: Reduced G6PD activity and increased serum MDA level might be the key cause of the early visual abnormalities like reduced CS function of the alcoholic subjects.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.007
  • Insights from Intoxicated Drosophila
    • Authors: Emily Petruccelli; Karla R. Kaun
      Abstract: Publication date: Available online 21 March 2018
      Author(s): Emily Petruccelli, Karla R. Kaun
      Our understanding of Alcohol Use Disorder (AUD), particularly alcohol’s effect in the nervous system, has unquestionably benefited from the use of model systems such as Drosophila melanogaster. Here, we briefly introduce the use of flies in alcohol research, and highlight the genetic accessibility and neurobiological contribution flies have made to our understanding of AUD. Future fly research offers unique opportunities for addressing unresolved questions in the alcohol field such as the neuromolecular and circuit basis for cravings and alcohol-induced neuroimmune dysfunction. This review strongly advocates for interdisciplinary approaches and translational collaborations with the united goal of tackling the major health problems associated with alcohol abuse and addiction.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.004
  • The gut microbiota: a new target in the management of alcohol dependence
    • Authors: Sophie Leclercq; Peter Stärkel; Nathalie M. Delzenne; Philippe de Timary
      Abstract: Publication date: Available online 20 March 2018
      Author(s): Sophie Leclercq, Peter Stärkel, Nathalie M. Delzenne, Philippe de Timary

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.005
  • Molecular tools to elucidate factors regulating alcohol use
    • Authors: Marian L. Logrip
      Abstract: Publication date: Available online 20 March 2018
      Author(s): Marian L. Logrip
      Alcohol use disorders (AUD) are pervasive societal problems, marked by high levels of alcohol intake and recidivism. Despite these common disease traits, individuals diagnosed with AUD display a range of disordered drinking and alcohol-related behaviors. The diversity in disease presentation, as well as the established polygenic nature of the disorder and complex neurocircuitry, speak to the variety in neurochemical changes resulting from alcohol intake that may differentially regulate alcohol-related behaviors. Investigations into the molecular adaptations responsible for maladaptive alcohol-related behavioral outcomes require an ever-evolving set of molecular tools to elucidate with increasing precision how alcohol alters behavior through neurochemical changes. This review highlights recent advances in molecular methodology, addressing how incorporation of these cutting-edge techniques not only may enhance current knowledge of the molecular bases of AUD, but also may facilitate identification of improved treatment targets that may be therapeutic in specific subpopulations of AUD individuals.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.006
  • Determination of the formation rate of phosphatidylethanol by
           phospholipase D (PLD) in blood and test of two selective PLD inhibitors
    • Authors: Alexandra Schröck; Anna Henzi; Peter Bütikofer; Stefan König; Wolfgang Weinmann
      Abstract: Publication date: Available online 20 March 2018
      Author(s): Alexandra Schröck, Anna Henzi, Peter Bütikofer, Stefan König, Wolfgang Weinmann
      Phosphatidylethanol (PEth) is an alcohol biomarker formed from phosphatidylcholine (PC) by the enzyme phospholipase D (PLD) in the presence of ethanol. A drinking study revealed individual differences in maximum PEth levels after drinking up to a targeted blood alcohol concentration (BAC) of 1 ‰. This seemed to be due to different PLD activities in the tested persons. Furthermore, post-sampling formation of PEth occurred in blood samples, still containing alcohol. Therefore, a standardized in-vitro test for measuring individual PEth formation rates was developed. Two PLD inhibitors were tested for their potency to inhibit post-sampling PEth formation. PEth-negative blood samples were collected from a volunteer. Ethanol was added in different concentrations (0.1 – 3 ‰ BAC) directly after blood sampling. The specimens were incubated at 37 °C. Aliquots were taken at the start of the incubation, and every hour until 8 hours after start of incubation, and one sample was taken on subsequent days over one week. PEth 16:0/18:1 and PEth 16:0/18:2 were determined by online-SPE-LC-MS/MS. Furthermore, this test system was applied to blood samples of 12 volunteers. For the inhibition tests, fresh blood (spiked with 1 ‰ ethanol) was spiked with 30, 300, 3000, 30000 nM of either halopemide or 5-fluoro-2-indolyl des-chlorohalopemide (FIPI), and incubated at 37 °C. PEth concentrations were determined hourly over 5 hours on the first day and once on day 2 and 3. PEth formation was linear in the first 7 hours of incubation and dependent on the alcohol concentration. The formation rates of PEth 16:0/18:1 were 0.002 μmol·L-1·h-1 (0.1 ‰ BAC), 0.016 μmol·L-1·h-1 (1 ‰ BAC), 0.025 μmol·L-1·h-1 (2 ‰ BAC) and 0.029 μmol·L-1·h-1 (3 ‰ BAC). For PEth 16:0/18:2, the formation rates were 0.002 μmol·L-1·h-1 (0.1 ‰ BAC), 0.019 μmol·L-1·h-1 (1 ‰ BAC), 0.025 μmol·L-1·h-1 (2 ‰ BAC) and 0.030 μmol·L-1·h-1 (3 ‰ BAC). Maximum concentrations reached 431 ng/mL (PEth 16:0/18:1) and 496 ng/mL (PEth 16:0/18:2) at 3 ‰ BAC after 3 days. Maximum velocity (vmax) was not reached under these conditions. PEth formation in blood of the 12 volunteers ranged between 0.011 – 0.025 μmol·L-1·h-1 for PEth 16:0/18:1 and between 0.014 – 0.021 μmol·L-1·h-1 for PEth 16:0/18:2. PEth formation in human blood was inhibited by halopemide in a concentration-dependent manner. However, a complete inhibition was not achieved by the applied maximum concentration of 30000 nM. FIPI showed a better inhibition of PEth formation. A complete inhibition could be achieved by a concentration of 30000 nM for the first 24 h (for PEth 16:0/18:1) and for 48 h (for PEth 16:0/18:2). Formation of PEth was found to be dependent on the BAC. As a consequence, it is essential to inhibit PLD activity after blood collection to avoid post-sampling formation of PEth in blood samples with a positive BAC. Inhibition of PEth formation was more effective using FIPI compared to halopemide.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.003
  • The Possible Mediating Effect of Alcohol Dependence on the Relationship
           between Adverse Childhood Experiences and Attempted Suicide
    • Authors: Wen-Yin Chen; Ying-Yeh Chen; Heng-Hsiu Liu; Po-Hsiu Kuo; Ming-Chyi Huang
      Abstract: Publication date: Available online 15 March 2018
      Author(s): Wen-Yin Chen, Ying-Yeh Chen, Heng-Hsiu Liu, Po-Hsiu Kuo, Ming-Chyi Huang
      Adverse childhood experiences (ACEs) and alcohol dependence (AD) carry independent risks for suicidal behavior. While the strength of the association between ACEs and attempted suicide is weakened following adjustment for AD, no study to date has directly performed to determine whether AD affects the risk of suicide attributable to ACEs. The study aimed to examine the possible role of alcohol dependence (AD) in the relationship between various ACEs and attempted suicide. This cross-sectional study assessed history of ACEs among 184 AD patients and 205 control participants using the Family Health Questionnaire. Lifetime history of attempted suicide was collected using the Chinese version of the Composite International Diagnostic Interview. We used Sobel test to examine the mediating effects of AD on the relationship between ACEs and attempted suicide. Results showed that the suicide attempters were associated with higher rates of AD and ACEs. The regression analysis showed AD and multiple ACEs exposure is independently associated with attempted suicide. AD appears as a partial mediator in the relationship between attempted suicide and specific type of ACE (exposure to a battered mother or sexual abuse) or exposure to ≧ 3 types of ACEs. We conclude that AD might partially mediate the associations detected between attempted suicide and exposure to a battered mother, sexual abuse, and ≧ 3 types of ACEs. These observations may provide important insight for intervention strategies aimed at reducing the risk of suicide attempts.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.002
  • Gene edited CRISPy Critters for alcohol research
    • Authors: Gregg E. Homanics
      Abstract: Publication date: Available online 7 March 2018
      Author(s): Gregg E. Homanics
      Genetically engineered animals are powerful tools that have provided invaluable insights into mechanisms of alcohol action and alcohol use disorder. Traditionally, production of gene targeted animals was a tremendously expensive, time consuming, and technically demanding undertaking. However, the recent advent of facile methods for editing the genome at very high efficiency is revolutionizing how these animals are made. While pioneering approaches to create gene edited animals first used zinc finger nucleases and subsequently transcription activator like effector nucleases, these approaches have been largely supplanted in an extremely short period of time with the recent discovery and precocious maturation of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system. CRISPR uses a short RNA sequence to guide a non-specific CRISPR associated nuclease (Cas) to a precise, single location in the genome. Because the CRISPR/Cas system can be cheaply, rapidly, and easily reprogrammed to target nearly any genomic locus of interest simply by recoding the sequence of the guide RNA, this gene editing system has been rapidly adopted by numerous labs around the world. With CRISPR/Cas, it is now possible to perform gene editing directly in early embryos from every species of animals that are of interest to the alcohol field. Techniques have been developed that enable the rapid production of animals in which a gene has been inactivated (knockout) or modified to harbor specific nucleotide changes (knockins). This system has also been used to insert specific DNA sequences such as reporter or recombinase genes into specific loci of interest. Genetically engineered animals created with the CRISPR/Cas system (CRISPy Critters) are being produced at an astounding pace. Animal production is no longer a significant bottleneck to new discoveries. CRISPy animal studies are just beginning to appear in the alcohol literature, but their use is expected to explode in the near future. CRISPy mice, rats, and other model organisms are sure to facilitate advances in our understanding of alcohol use disorder.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.03.001
  • Sex Differences in the Synergistic Effect of Prior Binge Drinking and
           Traumatic Stress on Subsequent Ethanol Intake and Neurochemical Responses
           in Adult C57BL/6J Mice
    • Authors: Deborah A. Finn; Melinda L. Helms; Michelle A. Nipper; Allison Cohen; Jeremiah J. Jensen; Leslie L. Devaud
      Abstract: Publication date: Available online 3 March 2018
      Author(s): Deborah A. Finn, Melinda L. Helms, Michelle A. Nipper, Allison Cohen, Jeremiah J. Jensen, Leslie L. Devaud
      Alcohol use disorders (AUDs) are characterized by repeated episodes of binge drinking. Based on reports that exposure to predator odor stress (PS) consistently increases ethanol intake, the present studies examined whether prior binge drinking differentially altered responsivity to PS and subsequent ethanol intake in male and female mice, when compared to mice without prior binge exposure. Initial studies in naïve male and female C57BL/6J mice confirmed that 30 min exposure to dirty rat bedding significantly increased plasma corticosterone (CORT) levels and anxiety-related behavior, justifying the use of dirty rat bedding as PS in the subsequent drinking studies. Next, separate groups of male and female C57BL/6J mice received 7 binge ethanol sessions (binge) or drank water (controls), followed by a 1 month period of abstinence. Then, 2-bottle choice ethanol intake (10% or 10E versus water, 23 h/day) was measured in lickometer chambers for 4 weeks. After baseline intake stabilized, exposure to intermittent PS (2X/week X 2 weeks) significantly enhanced ethanol intake after the 2nd PS in male, but not female, binge mice versus baseline and versus the increase in controls. However in a subgroup of females (with low baselines), PS produced a similar increase in 10E intake in control and binge mice versus baseline. Analysis of lick behavior determined that the enhanced 10E intake in binge male mice and in the female low baseline subgroup was associated with a significant increase in 10E bout frequency and 10E licks throughout the circadian dark phase. Thus, PS significantly increased 10E intake and had a synergistic interaction with prior binge drinking in males, whereas PS produced a similar significant increase in 10E intake in the low baseline subgroup of binge and control females. Plasma CORT levels were increased significantly in both binge and control animals after PS. CORT levels at 24 h withdrawal from daily 10E intake were highest in the groups with elevated 10E licks (i.e., binge males and control females). At 24 h withdrawal, protein levels of GABAA receptor α1 subunit, corticotropin releasing factor receptor 1, and glucocorticoid receptor in prefrontal cortex (PFC) and hippocampus (HC) were differentially altered in the male and female mice versus levels in separate groups of age-matched naïve mice, with more changes in HC than in PFC and in females than in males. Importantly, the sexually divergent changes in protein levels in PFC and HC add to evidence for sex differences in the neurochemical systems influenced by stress and binge drinking and argue for sex-specific pharmacological strategies to treat AUD.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.02.004
  • Nicotine affects ethanol-conditioned taste, but not place, aversion in a
           simultaneous conditioning procedure
    • Authors: Gregory C. Loney; Ricardo Marcos Pautassi; Delna Kapadia; Paul J. Meyer
      Abstract: Publication date: Available online 2 March 2018
      Author(s): Gregory C. Loney, Ricardo Marcos Pautassi, Delna Kapadia, Paul J. Meyer
      The conditioned taste aversion (CTA) induced by ethanol is a key factor limiting ethanol intake. Nicotine, a drug co-consumed with ethanol, may decrease this aversion by modulating the unconditioned effects of ethanol or by disrupting the association between ethanol and its associated cues. This study analyzed ethanol-induced CTA and conditioned place aversion (CPA) in Long Evans rats with sub-chronic exposure to nicotine. The rats were treated with nicotine (0.0 or 0.4 mg/kg) three times before conditioning (on lickometer training sessions three, four and five) and across conditioning days. During the conditioning the rats were given ethanol (1.3 g/kg) preceded and followed by presentation of a taste (NaCl) and tactile (rod or hole floors) conditioned stimuli (CS+), respectively. On CS- conditioning days, the rats were given vehicle and exposed to alternative stimuli. Three CTA and CPA testing sessions were then conducted. It was found that nicotine reduced ethanol-induced CTA and enhanced locomotor activity, but did not significantly modify the magnitude of ethanol-induced CPA. The effects of nicotine on CTA were observed during both conditioning and testing sessions, and were specific to the NaCl CS+, having no effect on reactivity to water. The dissociation between the effect of nicotine on ethanol-induced CTA and CPA suggests that nicotine does not alter ethanol’s motivational properties by generally increasing its positive rewarding effects; nor does it blunt all aversive-like responding to this drug. Instead, nicotine may impede ethanol-induced CTA induced by ethanol by disrupting the neural underpinnings of this specific form of associative learning.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.02.005
  • Effects of ethanol and varenicline on female Sprague-Dawley rats in a
           third trimester model of fetal alcohol syndrome
    • Authors: Karienn S. Montgomery; Eric A. Bancroft; Annette S. Fincher; Ewelina A. Migut; Vincent Provasek; David Murchison; Dustin W. DuBois
      Abstract: Publication date: Available online 2 March 2018
      Author(s): Karienn S. Montgomery, Eric A. Bancroft, Annette S. Fincher, Ewelina A. Migut, Vincent Provasek, David Murchison, Dustin W. DuBois
      Perinatal ethanol (EtOH) exposure disrupts a variety of developmental processes in neurons important for establishing a healthy brain. These EtOH-induced impairments known as fetal alcohol spectrum disorder (FASD) are not fully understood, and currently, there is no effective treatment. Further, growing evidence suggests that adult females are more susceptible to EtOH with the effects of perinatal EtOH exposure also being sexually divergent. Female models have been historically underutilized in neurophysiological investigations, but here, we used a third trimester binge-EtOH model of FASD to examine changes to basal forebrain (BF) physiology and behavior in female Sprague-Dawley rats. We also tested varenicline as a potential cholinomimetic therapeutic. Rat pups were gavage-treated with binge-like EtOH, varenicline and EtOH, and varenicline alone. Using patch clamp electrophysiology in BF slices, we observed that binge-EtOH exposure increased spontaneous post-synaptic current (sPSC) frequency. Varenicline exposure alone also enhanced sPSC frequency. Varenicline plus EtOH co-treatment prevented the sPSC frequency increase. Changes in BF synaptic transmission persisted into adolescence after binge-EtOH treatment. Behaviorally, binge-EtOH treated females displayed increased anxiety (thigmotaxis) and demonstrated learning deficits in the water maze. Varenicline/EtOH co-treatment was effective at reducing these behavioral deficits. In the open field, EtOH treated rats displayed longer distances traveled and spent less time in the center of the open field box. Co-treated rats displayed less anxiety demonstrating a possible effect of varenicline on this measure. In conclusion, EtOH-induced changes in both BF synaptic transmission and behavior were reduced by varenicline in female rats supporting a role for cholinergic therapeutics in FASD treatment.

      PubDate: 2018-04-11T01:05:04Z
      DOI: 10.1016/j.alcohol.2018.02.006
  • Instructions to Authors
    • Abstract: Publication date: March 2018
      Source:Alcohol, Volume 67

      PubDate: 2018-02-25T18:57:18Z
  • Sexual dimorphism in the neural impact of stress and alcohol
    • Authors: Marian L. Logrip; Verica Milivojevic; Megan L. Bertholomey; Mary M. Torregrossa
      Abstract: Publication date: Available online 23 February 2018
      Author(s): Marian L. Logrip, Verica Milivojevic, Megan L. Bertholomey, Mary M. Torregrossa
      Alcohol use disorder is a widespread mental illness characterized by periods of abstinence followed by recidivism, and stress is the primary trigger of relapse. Despite the higher prevalence of alcohol use disorder in males, the relationship between stress and behavioral features of relapse, such as craving, is stronger in females. Given the greater susceptibility of females to stress-related psychiatric disorders, understanding sexual dimorphism in the relationship between stress and alcohol use is essential to identifying better treatments for both male and female alcoholics. This review addresses sex differences in the impact of stressors on alcohol drinking and seeking in rodents and humans. As these behavioral differences in alcohol use and relapse originate from sexual dimorphism in neuronal function, the impact of stressors and alcohol, and their interaction, on molecular adaptations and neural activity in males and females will also be discussed. Together the data reviewed herein, arising from a symposium entitled “Sex matters in stress-alcohol interactions” presented at the Fourth Volterra Conference on Stress and Alcohol, will highlight the importance of identifying sex differences to improve treatments for comorbid stress and alcohol use disorder in both populations.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2018.02.002
  • Impact of a novel environment on alcohol-induced locomotor activity in
           Wistar rats
    • Authors: Fabiola Hernández-Vázquez; Cosette Reyes-Guzmán; Milagros Méndez
      Abstract: Publication date: Available online 17 February 2018
      Author(s): Fabiola Hernández-Vázquez, Cosette Reyes-Guzmán, Milagros Méndez
      Clinical studies have shown a positive correlation between novelty-seeking behavior and the susceptibility to consume drugs of abuse. Although several animal studies have demonstrated this correlation with psychostimulants or morphine, studies with alcohol have shown conflicting results. The aim of this work was to investigate alcohol-induced motor effects in Wistar rats with different responses to novelty. Animals were classified as Low- (LR) or High-Responders (HR) to novelty, depending on their horizontal activity in an automated open field. Motor activity was recorded in naïve, saline and alcohol-administered rats at different doses (0.1, 0.25, 0.5, 1.0 or 2.5 g/kg). Horizontal movements, rearings and stereotyped behaviors were evaluated. After the behavioral test, animals were sacrificed and blood alcohol concentrations (BACs) measured. Low (0.1 and 0.25 g/kg) and high (2.5 g/kg) alcohol doses decreased horizontal movements in LR animals, whereas 1.0 g/kg increased this parameter in HR rats. Rearings were increased by alcohol 1.0 g/kg in LR animals. In HR rats, alcohol doses of 0.5 and 1.0 g/kg also increased this parameter. Stereotypies were decreased by an alcohol dose of 2.5 g/kg in LR animals but were increased by an intermediate dose (1.0 g/kg) in HR rats. Differences in horizontal movements and rearings were found between LR and HR animals at certain ethanol doses. Horizontal movements (0.25 g/kg) and rearings (0.5 g/kg) were lower in LR than HR rats; however, rearings were lower in HR than LR rats at 1.0 g/kg. BACs were similar between LR and HR rats at all ethanol doses. These findings suggest that HR rats are more responsive to the stimulant effects of intermediate alcohol doses, whereas LR animals are sensitive to low-high doses of the drug. Sensitivity to alcohol motor effects may substantially depend on the initial animal’s response to a novel environment. The stimulant effects of alcohol may constitute important behavioral traits significantly associated with the rewarding properties of the drug.

      PubDate: 2018-02-25T18:57:18Z
      DOI: 10.1016/j.alcohol.2018.02.001
  • CRF modulation of central monoaminergic function: Implications for sex
           differences in alcohol drinking and anxiety
    • Authors: Kristen Elizabeth Pleil; Mary Jane Skelly
      Abstract: Publication date: Available online 2 February 2018
      Author(s): Kristen Elizabeth Pleil, Mary Jane Skelly
      Decades of research have described the importance of corticotropin-releasing factor (CRF) signaling in alcohol addiction, as well as in commonly co-expressed neuropsychiatric diseases including anxiety and mood disorders. However, CRF signaling can also acutely regulate binge alcohol consumption, anxiety, and affect in non-dependent animals, possibly via modulation of central monoaminergic signaling. We hypothesize that basal CRF tone is particularly high in animals and humans with an inherent propensity for high anxiety and alcohol consumption, and thus these individuals are at increased risk for the development of alcohol use disorder and comorbid neuropsychiatric diseases. The current review focuses on extrahypothalamic CRF circuits, particularly those stemming from the bed nucleus of the stria terminalis (BNST), found to play a role in basal phenotypes and examines whether the intrinsic hyperactivity of these circuits is sufficient to escalate the expression of these behaviors and steepen the trajectory of development of disease states. We focus our efforts on describing CRF modulation of biogenic amine neuron populations that have widespread projections to the forebrain to modulate behaviors including alcohol and drug intake, stress reactivity, and anxiety. Further, we review the known sex differences and estradiol modulation of these neuron populations and CRF signaling at their synapses to address the question of whether females are more susceptible to the development of comorbid addiction and stress-related neuropsychiatric diseases because of hyperactive extrahypothalamic CRF circuits compared to males.

      PubDate: 2018-02-05T10:43:57Z
      DOI: 10.1016/j.alcohol.2018.01.007
  • Forced ethanol ingestion by Wistar rats from a juvenile age increased
           voluntary alcohol consumption in adulthood, with the involvement of
    • Authors: Luis-Gabriel Mendoza-Ruiz; Priscila Vázquez-León; Lucía Martínez-Mota; Eduardo Ramírez San Juan; Abraham Miranda-Páez
      Abstract: Publication date: Available online 2 February 2018
      Author(s): Luis-Gabriel Mendoza-Ruiz, Priscila Vázquez-León, Lucía Martínez-Mota, Eduardo Ramírez San Juan, Abraham Miranda-Páez
      Human adolescents who drink alcohol are more likely to become alcoholics in adulthood. Alcohol administration (intraperitoneally) or drinking (in a 2-bottle free choice paradigm) during the juvenile/adolescent age of rats promotes voluntary alcohol consumption in adulthood. On the other hand, there is growing evidence that the orexinergic system plays a role in several rewarded behaviors, including alcohol ingestion. Since it is unknown what effect is exerted in adulthood by forced oral ethanol intake and/or administration of orexin-A (OX-A) in juvenile rats. The present study aimed to evaluate this question. A group of male Wistar rats was forced to drink ethanol (10% v/v) as the only liquid in the diet from weaning (postnatal day 21) to postnatal day 67 (46 days), followed by a forced withdrawal period. An age-matched group was raised drinking tap water (control). OX-A or its vehicle was microinjected intracerebroventricularly (icv) (1 nmol/0.6 μL) to explore its effect as well. Locomotor activity and voluntary ethanol consumption were later assessed in all groups. The rats forced to consume ethanol early in life showed an elevated level of ambulation and alcohol ingestion in adulthood. A single injection of OX-A increased locomotor activity and acute ethanol intake in rats with or without prior exposure to alcohol at the juvenile stage. In conclusion, forced ethanol consumption in juvenile rats led to increased voluntary alcohol drinking behavior during adulthood, an effect likely facilitated by OX-A.

      PubDate: 2018-02-05T10:43:57Z
      DOI: 10.1016/j.alcohol.2018.01.008
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