Effects of MK-801 on clozapine-induced potentiation of excitatory synaptic responses in the perforant path-dentate gyrus pathway in chronically prepared rabbits.

摘要

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.