NEFIRACETAM (DM-9384) REVERSES APOMORPHINE-INDUCED AMNESIA OF A PASSIVE-AVOIDANCE RESPONSE - DELAYED EMERGENCE OF THE MEMORY RETENTION EFFECTS

Nefiracetam is a novel pyrrolidone derivative which attenuates scopola mine-induced learning and post-training consolidation deficits. Given that apomorphine inhibits passive avoidance retention when given durin g training or in a defined 10-12h post-training period, we evaluated t he ability of nefiracetam to attenuate amnesia induced by dopaminergic agonism. A step-down passive avoidance paradigm was employed and nefi racetam (3 mg/kg) and apomorphine (0.5 mg/kg) were given alone or in c ombination during training and at the 10-12h post-training period of c onsolidation. Go-administration of nefiracetam and apomorphine during training or 10h thereafter produced no significant anti-amnesic effect . However, administration of nefiracetam during training completely re versed the amnesia induced by apomorphine at the 10h post-training tim e and the converse was also true. These effects were not mediated by a dopaminergic mechanism as nefiracetam, at millimolar concentrations, failed to displace either [H-3]SCH 23390 or [H-3]spiperone binding fro m D-1 or D-2 dopamine receptor subtypes, respectively. It is suggested that nefiracetam augments molecular processes in the early stages of events which ultimately lead to consolidation of memory.