Paternal alcohol exposure attenuates maintenance and reinstated operant responding for alcohol in the offspring of rats

Background: The heritability of alcohol use disorder is close to 50%, yet common genetic variants account for less than 5% of risk. The missing heritability may reflect environmental exposure in the parents prior to conception. Indeed, paternal alcohol exposure has many behavioral and biological consequences for rodent offspring. We recently found that paternal alcohol exposure attenuated the acquisition of operant alcohol self-administration in offspring of rats of both sexes. Here we test whether this effect extends to other phases of operant self-administration thought to model motivation, craving, and relapse. Methods: Wistar male rats exposed to alcohol vapors or air for 6 weeks were mated with alcohol-naive females 8 weeks later. The adult offspring were trained to lever press for alcohol and tested under several conditions: (1) maintenance responding under a progressive ratio schedule, (2) extinction responding due to removal of the alcohol delivery contingency, (3) reinstatement of extinguished responding in the presence of alcohol-associated cues, and (4) reinitiation of lever press responding for alcohol delivery under fixed and progressive ratio schedules. Results: Alcohol-sired offspring showed reduced responding under the progressive ratio schedule and blunted cue-induced reinstatement of extinguished responding. Alcohol-sired offspring also emitted fewer responses during extinction sessions and did not reinitiate responding to the same extent as control-sired rats after alcohol delivery was restored. Conclusions: Across all conditions, paternal alcohol exposure led to a reduction in the reinforcing effects of alcohol in offspring. These results are consistent with studies conducted with paternal cocaine exposure except that here we find effects in rats of both sexes.