The offspring of alcohol-exposed sires exhibit heightened ethanol intake and behavioral alterations in the elevated plus maze

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2021-05, Vol.92, p.65-72
• Main Authors: Koabel, Jennifer, McNivens, Meghan, McKee, Paul, Pautassi, Ricardo, Bordner, Kelly, Nizhnikov, Michael
• Format: Article
• Language: English
• Subjects: Alcohol use; Anxiety; Behavior; Drug dosages; Epigenetics; Ethanol; Families & family life; Females; Gene expression; inhibitory control; Males; Offspring; paternal exposure; Teenagers; transgenerational
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2021.01.009

Research suggests that addictive traits are indeed heritable, but very few preclinical studies have explored transgenerational effects of paternal alcohol exposure. The present study addressed this gap in knowledge. We explored whether offspring of ethanol-exposed sires would be more likely to accept ethanol than descendants of water-exposed and control sires. We also investigated whether the second generation of ethanol-exposed descendants would accept ethanol more than controls and were more or less likely to experience anxiety-like behavior in behavioral assessments. We exposed male rats to repeated binge doses of alcohol (4 g/kg/day across 8 days), water, or left them untreated and mated them with untreated females. We then bred the offspring of these rats to test transgenerational effects of paternal alcohol exposure. We tested 14-day-old offspring from the first and second filial generation for their acceptance of ethanol and water, and measured anxiety-like behavior in 38-day-old, second-generation offspring using an elevated plus maze. The results indicate that offspring of ethanol-exposed sires increase ethanol acceptance in the first generation compared to untreated controls, whereas in the second-generation increased ethanol acceptance vs. these controls is seen in descendants of both ethanol- and vehicle-treated sires. At adolescence, the second generation of rats derived from alcohol-exposed sires exhibited significantly more time spent in the open arms and significantly more arm entries than any other group. The present study suggests that parental ethanol exposure is associated with lingering effects in the infant and adolescent offspring. The second filial generation was also found to be affected, albeit similarly by grandparental ethanol exposure or by the stress of the vehicle administration. •Paternal alcohol affects inhibitory control of offspring.•Paternal alcohol increases acceptance of ethanol in infancy across two generations.•Paternal stress increases acceptance of ethanol in infancy in the second generation.