Clozapine-induced potentiation of synaptic responses in the perforant path-dentate gyrus pathway in chronically prepared rabbits

Abstract

To examine the contribution of N-methyl- d-aspartate (NMDA) receptors in the mechanisms underlying the action of antipsychotics, we investigated the effects of a representative atypical antipsychotic, clozapine (CLZ), on the induction of long-term potentiation (LTP) in the perforant path-dentate gyrus pathway in 15 chronically prepared rabbits. Eventually, neither low (10 mg/kg) nor high (20 mg/kg) doses of CLZ intraperitoneally injected had any effects on LTP induction. However, the high dose CLZ always potentiated the ordinary synaptic responses induced by single stimulations before the LTP induction. The present study indicates a new finding, the presence of ‘CLZ-induced potentiation’, although it needs further investigation whether NMDA receptors contribute to this potentiation.