Nefiracetam (DM-9384) preserves hippocampal neural cell adhesion molecule-mediated memory consolidation processes during scopolamine disruption of passive avoidance training in the rat.
Scopolamine (0.15 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.
Department of Pharmacology, University College, Dublin, Ireland.
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Doyle
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Regan
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Shiotani
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism / Q000502:physiology*; D006001:Glycoconjugates / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D011619:Psychotropic Drugs / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology*; D012794:Sialic Acids / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D006001:Glycoconjugates; D011619:Psychotropic Drugs; D011760:Pyrrolidinones; D012794:Sialic Acids; C058876:nefiracetam; D012601:Scopolamine