Effects of early maternal separation on ethanol intake, GABA receptors and metabolizing enzymes in adult rats

Rationale: Maternal separation (MS) in neonatal rats affects ethanol self-administration (SA) in adulthood; however, the conditions and mechanisms need to be clarified. Objectives: The goal of this study was to determine the effect of MS on ethanol SA in adulthood in different groups of rats, which control for time of separation, handling, and rearing conditions and, for mechanistic assessment, to examine GABA-A receptors in the central nucleus of the amygdala (CeA) and levels of liver metabolizing enzymes. Methods: Newborn, male Long-Evans rats were randomly assigned to different groups and treated over postnatal days 2-14. The rats were picked up by their tails and put back down with no separation (MS0), separated from their mother for 15 min/day (MS15), separated from their mother for 180 min/day (MS 180), handled once for a bedding change (NH), or were animal facility reared (AFR). In adulthood, these rats were allowed 5-day continuous access to ethanol, and GABA-A receptors and liver enzymes were measured. Results: The MS15 group consumed and preferred significantly less ethanol (about one third) than the MS180 group; however, neither group was different from the MS0 or the AFR group. The NH group consumed and preferred significantly more ethanol than all other groups, at least twice that of the MS180s. GABA-A receptors were increased in the CeA in MS15s, which could help explain the effects. Alcohol dehydrogenase may have been altered in the AFRs. Conclusions: Various treatments in neonates affect ethanol intake and GABA-A receptors, and possibly ethanol metabolism, in adulthood. These changes were not simply related to time of separation but were also due to the degree of handling.