Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice.
A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol-drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring.
Center for Neuroscience, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
Gregory R
GR
Rompala
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
Andrey
A
Finegersh
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.
Gregg E
GE
Homanics
D000428:Alcohol Drinking / Q000009:adverse effects / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018812:Paternal Exposure / Q000009:adverse effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D059606:Polydipsia / Q000378:metabolism* / Q000523:psychology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
D000431:Ethanol
Alcohol drinking; Corticosterone; Epigenetics; HPA-axis; Intergenerational; Polydipsia