Abstract
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 naïve 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.
Highlights
Alcohol use disorder poses a major social and economic burden to society, accounting for approximately 5.9% of deaths worldwide in 2012.1 In humans, twin and adoption studies have implicated both genetic and environmental factors in the heritability of this disorder.[2]
The degree of genetic predisposition to alcohol use disorder can vary depending on religion or marital status,[4,5,6] implicating important interactions between genes and environment to modulate the propensity for alcohol abuse
We show that exposure of sires to voluntary alcohol self-administration prior to mating reduced alcohol-seeking behavior in male offspring
Summary
Alcohol use disorder poses a major social and economic burden to society, accounting for approximately 5.9% of deaths worldwide in 2012.1 In humans, twin and adoption studies have implicated both genetic and environmental factors in the heritability of this disorder.[2]. There is evidence suggesting that paternal alcohol abuse prior to conception can impact the behavior of future generations Both acute and chronic alcohol exposure prior to mating in mice results in hyperactivity, inattention, impulsivity, developmental delays, and increased aggression in both male and female offspring.[13,14] the relationship between paternal alcohol exposure and intergenerational effects on offspring alcoholrelated behaviors and behavioral sensitivity to alcohol is an understudied topic. The paternal alcohol exposure studies to date have not used voluntary self-administration paradigms to examine offspring alcohol-related behaviors These experiments were conducted in a bid to improve our models of paternal inheritance of addictive-like phenotypes, as well as increase face and construct validity. We chose inbred rats deliberately to enable clear assessment of gene x environment interactions, since altered offspring endophenotypes must presumably reflect epigenetic modification.[18,19] Behaviorally, we used the context-induced relapse after punishmentimposed abstinence procedure[20] to assess alcohol self-administration, punishment, and context-induced relapse in offspring of alcohol-experienced sires
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