Developmental influence of gonadal function on the anxiolytic effect of diazepam on environment-related social interaction in the male rat.

This study examined the anxiolytic action of diazepam (DZ) on environment-induced changes in social interaction (SI) in rats as a function of pubertal age. SI in pairs of male rats was measured in a familiar and an unfamiliar environment. Control (gonadally-intact) male rats received daily injections of vehicle or DZ (0.5 or 1.0 mg/kg) for 5 consecutive days and then were tested for SI at 28, 35, or 60 days of age. A differential impact of the two environments on SI was evident in control rats at 35 and 60 days, but not at 28 days. However, DZ modified SI only at 60 days. Based on these findings, the influence of gonadal androgens on the development of DZ modulation of SI was then evaluated. The anxiolytic action of DZ on SI was present in precocious rats tested at 35 days and in rats castrated in adulthood. These results suggest that gonadal androgens are necessary for the development of modifiability by DZ of SI, but not for the anxiolytic effect of DZ in the adult rat. Furthermore, while castration of rats as juveniles (day 19) altered the effect of DZ on SI in adult rats, testosterone replacement during puberty (days 30 to 60) reinstated the ability of DZ to modify SI. The results of these studies demonstrate that gonadal function during puberty is necessary for the development of specific neural systems underlying SI in the adult. These neural systems, perhaps unlike those underlying environment-specific SI at younger ages, are influenced by DZ. Finally, gonadal androgens appear to exert an organizational influence but not an activational effect on DZ modulation of SI.