title: Paternal preconception alcohol exposure imparts intergenerational alcohol-related behaviors to male offspring on a pure C57BL/6J background.
abstract: While alcohol use disorder (AUD) is a highly heritable condition, the basis of AUD in families with a history of alcoholism is difficult to explain by genetic variation alone. Emerging evidence suggests that parental experience prior to conception can affect inheritance of complex behaviors in offspring via non-genomic (epigenetic) mechanisms. For instance, male C57BL/6J (B6) mice exposed to chronic intermittent vapor ethanol (CIE) prior to mating with Strain 129S1/SvImJ ethanol-naïve females produce male offspring with reduced ethanol-drinking preference, increased ethanol sensitivity, and increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). In the present study, we tested the hypothesis that these intergenerational effects of paternal CIE are reproducible in male offspring on an inbred B6 background. To this end, B6 males were exposed to 6 weeks of CIE (or room air as a control) before mating with ethanol-naïve B6 females to produce ethanol (E)-sired and control (C)-sired male and female offspring. We observed a sex-specific effect, as E-sired males exhibited decreased two-bottle free-choice ethanol-drinking preference, increased sensitivity to the anxiolytic effects of ethanol, and increased VTA BDNF expression; no differences were observed in female offspring. These findings confirm and extend our previous results by demonstrating that the effects of paternal preconception ethanol are reproducible using genetically identical, inbred B6 animals.
authors.affiliation: Center for Neuroscience, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA. Electronic address: grr14@pitt.edu.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Rompala
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA. Electronic address: afinegersh@ucsd.edu.
authors.forename: Andrey
authors.initials: A
authors.lastname: Finegersh
authors.affiliation: Department of Neuroscience, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA. Electronic address: mas486@pitt.edu.
authors.forename: Michelle
authors.initials: M
authors.lastname: Slater
authors.affiliation: Center for Neuroscience, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA; Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA; Department of Anesthesiology, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA. Electronic address: homanicsge@anes.upmc.edu.
authors.forename: Gregg E
authors.initials: GE
authors.lastname: Homanics
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000633:toxicity*; D001007:Anxiety / Q000235:genetics / Q000517:prevention & control / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D020022:Genetic Predisposition to Disease; D040941:Heredity; D019570:Inhalation Exposure; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D010375:Pedigree; D012737:Sex Factors; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D019208:Brain-Derived Neurotrophic Factor; D000431:Ethanol
keywords: Alcohol drinking; Alcohol sensitivity; BDNF; Chronic intermittent vapor ethanol; Epigenetics; Stress