The kappa opioid system mediates gene -environment interaction effects on voluntary alcohol consumption in female rats

Genetic and environmental factors interact to influence vulnerability to neuropsychiatric disorders such as alcoholism. However, the mechanisms mediating gene-environment interaction are not well known, and few naturalistic models relevant to alcohol have been developed. To address these issues, behavioral observations were conducted with undisturbed in-fostered and cross-fostered Fischer and Lewis rat litters. As adults, the offspring received 1 mg/kg of the kappa opioid antagonist nor-BNI or vehicle followed by an oral self-administration regimen with continuous access to water and ethanol (four days each of 2, 4, 8 and 12%). Fischer dams engaged in more arched-back nursing and pup licking/grooming than Lewis. Alcohol self-administration varied by strain and concentration, with the most noteworthy effects at 8% where the in-fostered Lewis consumed more than the in-fostered Fischer: The Fischers were not affected by cross-fostering, but the Fischer maternal environment significantly reduced self-administration in Lewis rats. This gene-environment interaction effect was completely reversed by pretreatment with nor-BNI. In different animals, Lewis had higher blood alcohol concentrations and hypothermic responses to acute 1.25 g/kg ethanol, with no cross-fostering or nor-BNI effects. The cross-fostered Lewis exhibited the strongest conditioned taste aversions to 1.25 g/kg ethanol, which were unaltered by nor-BNI. Individual differences in active maternal care correlated negatively with self-administration of 8% alcohol in Lewis but not Fischer offspring; these relationships were nullified by nor-BNI. The role of the kappa opioid system in ethanol's motivational effects was considered as well as the implications of using inbred strains for the study of epigenetics and gene-environment interactions.