GONADAL STATUS AND PUBERTAL AGE INFLUENCE THE RESPONSIVENESS OF THE BENZODIAZEPINE GABA RECEPTOR COMPLEX TO ENVIRONMENTAL CHALLENGE IN MALE-RATS

Pubertal age and gonadal status in male rats influenced the functional response of the benzodiazepine (BZD)/GABA receptor chloride channel complex to an environmental challenge, i.e., encountering a stranger in a familiar versus an unfamiliar environment. Chloride (Cl-) enhancement of [H-3]flunitrazepam ([H-3]Flu) binding was facilitated by exposure to an unfamiliar environment relative to that measured in response to a familiar environment in gonadally intact adult rats but not in prepubertal rats (28 days). Enhancement of [H-3]Flu by Cl- at 28 days was not differentially affected by the two environments and did not differ from that measured in non-handled control rats at this age. While a differential effect of the two environments on Cl- enhancement of [H-3]Flu binding was also present in adult rats castrated as juveniles (at 19 days), the relationship of environmental challenge to Cl- facilitation was the reverse of that measured in intact adult rats. In addition, GABA-mediated Cl-36- uptake was facilitated in intact adult rats tested in either the familiar or unfamiliar environment relative to non-handled intact adult rats. This change in GABA-gated chloride channel function in response to environmental challenge, however, was not present in adult rats castrated as juveniles nor in 28-day-old rats. Therefore, both pubertal age and gonadal status influenced the responsiveness of the BZD/GABA receptor complex to environmental challenge. These findings suggest that pubertal development and adult hormonal status are important determinants of the functional responsiveness of the BZD/GABA receptor complex to environmental challenge.