Reduced alcohol-seeking in male offspring of sires exposed to alcohol self-administration followed by punishment-imposed abstinence

Emerging evidence has demonstrated that paternal alcohol use can modify the behavior of offspring, particularly male offspring. However, preclinical studies to date have not used voluntary self-administration of alcohol to examine alcohol-related behaviors in offspring. Here, we tested the hypothesis that paternal alcohol self-administration followed by punishment-imposed abstinence alters alcohol consumption and seeking in male offspring. Male inbred alcohol preferring iP rats were trained to self-administer alcohol in one context followed by punishment-imposed suppression of alcohol-seeking in a different context using contingent footshock. Following this, all rats were bred with alcohol naive female iP rats. F1 offspring were then trained to self-administer alcohol in an identical operant paradigm as sires. Alcohol intake and self-administration behaviors of alcohol-sired offspring were compared to control-sired offspring whose fathers had not been exposed to the alcohol operant conditioning experience. We found that paternal alcohol self-administration reduced context-induced relapse to alcohol-seeking in male offspring. These findings indicate that voluntary paternal alcohol experience, operant conditioning, and punishment can result in intergenerational changes in offspring behavior, and that this effect may protect against the vulnerability to relapse after alcohol use. We also noted reduced alcohol responding in the punishment-associated context in alcohol-sired offspring, suggesting altered perception of punishment sensitivity or the anxiogenic response to footshock. Collectively, these findings provide evidence that paternal alcohol abuse can impact alcohol-related behaviors in male offspring.