Bicuculline administered into the amygdala after training blocks benzodiazepine-induced amnesia.

Male Sprague-Dawley rats were injected (i.p.) with either midazolam (MDZ, 2.0 mg/kg) or vehicle (1.0 ml/kg) 10 min before they were trained on a multiple-trial inhibitory avoidance task. Immediately following the training, bicuculline methiodide (BMI; 2.0, 5.6, 56.0 or 197.0 pmol/0.5 microl) or vehicle (0.5 microl) was infused bilaterally into the amygdala. On a 48 h retention test the performance of the MDZ-treated animals was significantly poorer than that of controls. The retention of MDZ-treated animals given intra-amygdala injections of the lowest dose of BMI (2.0 pmol) was comparable to that of controls, whereas higher doses of BMI impaired retention. The present results are consistent with other findings indicating that the amygdala mediates the amnestic effects of benzodiazepines on aversive learning. Furthermore, these data suggest that benzodiazepines impair memory by disrupting post-training processes underlying memory consolidation.