This study was designed to determine whether psychological stress alters the function of the GABAergic synapse, examined as biochemical changes of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding, in unwashed membranes of rat cerebral cortex. Psychological stress increased the number of [35S]TBPS binding sites by 22%. This enhancement was very similar to that after acute foot shock (24%). Psychological stress was induced very rapidly, because only 1 day after previous foot shock exposure, [35S]TBPS binding was increased by 23%. Diazepam [3 mg/kg intraperitoneally (subcutaneously)] and ipsapirone (5 mg/kg subcutaneously), injected 30 min before psychological stress, antagonized the enhancement of [35S]TBPS binding. This result suggests that psychological stress is a good animal model for investigating the various biochemical changes related to stress, avoiding the physical components associated with most of the normally used stressors and mimicking only emotional state alterations.