NEFIRACETAM (DM-9384) PRESERVES HIPPOCAMPAL NEURAL CELL-ADHESION MOLECULE-MEDIATED MEMORY CONSOLIDATION PROCESSES DURING SCOPOLAMINE DISRUPTION OF PASSIVE-AVOIDANCE TRAINING IN THE RAT

Scopolamine (0. 1 5 mg/kg), a muscarinic antagonist, when administered during training or at a discrete 6-h posttraining time point, is demonstrated to inhibit the recall of a step-down passive avoidance response when tested at 24 and 48 h after task acquisition. Nefiracetam (3 mg/kg), a piracetam-related nootropic, when given with scopolamine during training tended to improve task recall, and this effect was more pronounced when given at the 6-h posttraining time. Co-administration of nefiracetam with scopolamine was not necessary to achieve the antiamnesic action, as nefiracetam given during training significantly improved the memory deficits produced by scopolamine at the 6-h posttraining time. The paradigm-specific increase in hippocampal neural cell adhesion molecule sialylation, which is observed during consolidation of a passive avoidance response, was attenuated by the presence of scopolamine during training and at the 6-h posttraining time, and this effect was reversed by co-administration of nefiracetam, albeit in a paradigm-independent manner. These results suggest nefiracetam exerts a neurotrophic action that protects memory consolidation from drug interventive insults.