Effects of MK-801 on clozapine-induced potentiation of excitatory synaptic responses in the perforant path-dentate gyrus pathway in chronically prepared rabbits.
We previously found that the atypical antipsychotic drug, clozapine, when intraperitoneally (i.p.) injected, long-lastingly potentiated excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulations to the perforant path in chronically prepared rabbits, and called this phenomenon 'clozapine-induced potentiation'. In the present study, we likewise examined whether clozapine-induced potentiation is caused by NMDA receptor-mediated neurotransmission in the perforant path-dentate gyrus pathway of chronically prepared rabbits. The non-competitive NMDA receptor antagonist - 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imino hydrogen maleate (MK-801; 1.0 mg/kg, i.p.) - completely prevented the potentiation of synaptic responses induced by subsequent administration of 20 mg/kg clozapine, whereas the 0.5 mg/kg dose had virtually no effect on the potentiation. These results suggest that the effect of clozapine requires NMDA receptor activation.
Kubota
T
T
Department of Neuropsychiatry Kanazawa Medical University, 1-1, Daigaku, Uchinada-machi, Kahoku-gun, Kanazawa, Japan. t-kubota@kanazawa-med.ac.jp
Jibiki
I
I
Enokido
F
F
Nakagawa
H
H
Watanabe
K
K
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D019580:Perforant Pathway / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D003024:Clozapine