Nefiracetam induces a long-lasting facilitation of hippocampal postsynaptic responses in mice lacking the NMDA receptor epsilon1 subunit.
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.
Matsumoto
Shinji
S
Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
Kanno
Takeshi
T
Nomura
Tamotsu
T
Shiotani
Tadashi
T
Watabe
Sigeo
S
Nabeshima
Toshitaka
T
Nishizaki
Tomoyuki
T
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D019580:Perforant Pathway / Q000187:drug effects / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D018696:Neuroprotective Agents; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; C058876:nefiracetam