Benzodiazepine impairs and beta-carboline enhances performance in learning and memory tasks.

Benzodiazepines are widely used anxiolytics and anticonvulsants, and their potent sedative properties are routinely used in presurgical anaesthesia. However, they are also known to induce a strong anterograde amnesia in patients. Specific benzodiazepine antagonists have recently been described, some of which have intrinsic pharmacological properties that are opposite to those of benzodiazepines. These have been called inverse agonists and they have been shown to be proconvulsant or convulsant whereas benzodiazepines are anticonvulsants. Inverse agonists are also anxiogenic rather than anxiolytic. Since benzodiazepines induce anterograde amnesia, we have investigated the possibility that inverse agonists might also have an opposite effect for this property and so enhance acquisition (learning) and (or) retention (memory). We report here that, in three different animal models, an inverse agonist of the beta-carboline group, methyl beta-carboline-3-carboxylate (beta-CCM), enhances animal performance in three different tasks used to investigate learning and memory.