Effects of zotepine on excitatory synaptic responses in the perforant path-dentate gyrus pathway in chronically prepared rabbits.

The effects of an atypical antipsychotic drug, zotepine, were examined on excitatory synaptic responses elicited in the dentate gyrus by single electrical stimulation of the perforant path and the induction of long-term potentiation in this pathway in chronically prepared rabbits. Doses of 1.0, 2.0 and 5.0 mg/kg of zotepine intraperitoneally injected had virtually no effect on the excitatory synaptic responses. However, these doses of zotepine dose dependently suppressed the induction of long-term potentiation. According to our previous studies, these results indicate that the effects of zotepine are different from those of the other atypical antipsychotic drugs, clozapine, but are rather similar to those of a typical antipsychotic drug, haloperidol and the 5-HT-dopamine receptor antagonist, risperidone. Furthermore, the zotepine-induced blockade of long-term potentiation induction may be associated with drug-induced cognitive dysfunction such as memory disturbance.