AbstractThe effect of the benzodiazepine‐receptor antagonist flumazenil on the facilitatory effect of (−)‐nicotine on memory in septal‐lesioned rats in a spatial task and in the inhibitory avoidance test in mice was investigated. In the two‐platform spatial discrimination test, septallesioned rats exhibited a significant number of errors in comparison to sham animals, an effect that can be reversed by the administration of (−)‐nicotine during the training phase. Flumazenil did not affect the performance of septal‐lesioned rats but it blocked the facilitatory effect of (–)‐nicotine on lesioned rats. In the inhibitory avoidance test in mice,(−)‐nicotine as well as flumazenil facilitated retention of the test at 0.62 and 10 μmol/kg, respectively. However, a low‐noneffective dose of flumazenil blocked the memory enhancing effect of (−)‐nicotine. The blockade of the facilitatory effect of (−)‐nicotine by flumazenil in normal and septal‐lesioned animals suggests that the cognitive effect of (−)‐nicotine requires the activation of benzodia