Involvement of benzodiazepine/GABA-A receptor complex in ethanol-induced state-dependent learning in rats.

State-dependent learning (SDL) induced by ethanol (EtOH) was investigated on the step-through passive avoidance task in rats. Pretraining injection of EtOH dose-dependently reduced step-through latency in the test session 24 h after the training. Injection of EtOH (1.0 g/kg) before both the training and test sessions, however, failed to reduce the latency. These results show that EtOH produces SDL. The failure of learning performance in SDL (dissociation in SDL) induced by EtOH was blocked by bicuculline, Ro15-4513 and picrotoxin injected before the training session. The success of learning performance in SDL (non-dissociation in SDL) induced by EtOH was also blocked by bicuculline, Ro15-4513 and picrotoxin injected before the test session. The antagonism of Ro15-4513 against EtOH was blocked by flumazenil. In the substitution test, pretest injection of EtOH produced non-dissociation in SDL in the both of pretraining diazepam-and muscimol-treated rats. On the other hand, neither pretest injection of diazepam nor muscimol produced non-dissociation in the pretraining EtOH-treated rats: asymmetrical cross-substitution between EtOH and diazepam and between EtOH and muscimol was observed. These results suggest that the EtOH-induced SDL is partially mediated by the benzodiazepine (BDZ)/GABA-A receptor complex.