A 'long-term-potentiation-like' facilitation of hippocampal synaptic transmission induced by the nootropic nefiracetam.
Nefiracetam, a nootropic agent, enhanced the slope of field excitatory postsynaptic potentials in the CA1 region of rat hippocampal slices to about 170% of basal levels, being evident still at 4-h washing-out of the drug. A similar sustained enhancement (>/=16 h after i.m. injection with nefiracetam) was observed in the population spikes recorded from the granular cell layer of the intact mouse hippocampus. Saturation of the enhancement in the synaptic strength occluded potentiation obtained with long-term potentiation (LTP) induced by high-frequency (tetanic) stimulation, and vice versa. Interestingly, the facilitatory action of nefiracetam was blocked by either the nicotinic acetylcholine (ACh) receptor antagonists, alpha-bungarotoxin and mecamylamine, or the selective protein kinase C (PKC) inhibitor, GF109203X, but in contrast, it was not affected by D-2-amino-5-phosphonovaleric acid (APV), a selective N-methyl-D-aspartate (NMDA) receptor antagonist. The results of the present study suggest that nefiracetam, whereas the action is independent of NMDA receptors, induces an 'LTP-like' facilitation of hippocampal synaptic transmission as a consequence of modulation of nicotinic ACh receptors and PKC. This may represent a likely mechanism underlying the cognition-enhancing actions of nefiracetam.
Nishizaki
T
T
Department of Physiology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. tomo@med.kobe-u.ac.jp
Matsuoka
T
T
Nomura
T
T
Matsuyama
S
S
Watabe
S
S
Shiotani
T
T
Yoshii
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008301:Maleimides / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology; D013449:Sulfonamides; D009435:Synaptic Transmission / Q000187:drug effects*
D002038:Bungarotoxins; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D018733:Nicotinic Antagonists; D018697:Nootropic Agents; D011760:Pyrrolidinones; D011978:Receptors, Nicotinic; D013449:Sulfonamides; C058876:nefiracetam; D016202:N-Methylaspartate; D008464:Mecamylamine; D015763:2-Amino-5-phosphonovalerate; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D007608:Kainic Acid; D001640:Bicuculline