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Nefiracetam induces a long-lasting facilitation of hippocampal postsynaptic responses in mice lacking the NMDA receptor epsilon1 subunit

Matsumoto, S.; Kanno, T.; Nomura, T.; Shiotani, T.; Watabe, S.; Nabeshima, T.; Nishizaki, T.

Brain Research 956(1): 178-181

2002


ISSN/ISBN: 0006-8993
PMID: 12426061
DOI: 10.1016/s0006-8993(02)03556-4
Accession: 011041714

The present study was designed to assess whether the facilitatory action of nefiracetam, a pyrrolidone derivative, on hippocampal postsynaptic responses is dependent upon N-methyl-D-aspartate (NMDA) receptors or not, by monitoring population spikes (PSs) in the dentate gyrus of hippocampal slices from mice lacking the NMDA receptor epsilon1 subunit. Nefiracetam (1 microM) induced a sustained facilitation of postsynaptic responses in the dentate gyrus of hippocampal slices from wild-type mice. The facilitation occluded the potentiation induced by high-frequency stimulation at the perforant path, and vice versa, suggesting a common mechanism between them. The perforant path long-term potentiation (LTP) was not induced in epsilon1 subunit knock-out mice, but nefiracetam (1 microM) persistently potentiated PS amplitude, reaching 280% of basal levels 50 min after 10-min treatment, similar to the potentiation achieved with wild-type mice. The results of the present study, thus, suggest that nefiracetam exerts its facilitatory action on hippocampal postsynaptic responses in an NMDA receptor-independent manner.

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