Methyl beta-carboline-3-carboxylate enhances performance in a multiple-trial learning task in mice.

In contrast to diazepam, a benzodiazepine receptor (BZ-R) ligand, which impairs memory processing, methyl beta-carboline-3-carboxylate (beta-CCM), another BZ-R ligand, administered before a training session, enhances performance in a retention test. This action, however, has only been demonstrated in single trial or single session learning protocols. The present report extends these results to a multiple-trial learning procedure in mice (brightness discrimination in a T-maze with negative reinforcement). The animals were trained for sessions of ten trials per day for six consecutive days. In a first experiment, the sessions during the first three days took place after administration of beta-CCM (0.3 mg/kg), diazepam (2.5 mg/kg) or saline. In a second experiment, especially designed to study the effects of beta-CCM, during the first three days animals received beta-CCM (0.3 mg/kg), Ro 15-1788 (15 mg/kg), beta-CCM + Ro 15-1788, vehicles of these drugs or saline. In the first experiment, performance was improved by beta-CCM and impaired by diazepam in the first three sessions as well as in the final three. In the second experiment, beta-CCM alone, as well as Ro 15-1788 improved performance, and the simultaneous administration of the two drugs suppressed these effects. These results suggest that the performance enhancing effects of beta-CCM observed in single trial learning protocols, during the retention test, can already be observed during drug treatment. They confirm that beta-CCM has an action on acquisition (learning). As the effects of beta-CCM are suppressed by the simultaneous administration of Ro 15-1788, our results could suggest a role for benzodiazepine receptors in learning. This question is discussed.