Effect of intraperitoneal injection of clozapine on pentylenetetrazole-kindled rats

Clozapine is one of the atypical antipsychotic drugs that is efficacious in patients unresponsive to typical antipsychotics. There are controversial evidences on convulsive effects of clozapine. This study was carried out to assess the effect of clozapine on seizures pentylenetetrazole-induced kindling in Wistar rats. In this experimental research 40 Wistar rats were randomly assigned to five groups. For the induction of kindling, pentylenetetrazole (45 mg/kg, ip) was administrated to rats. Animals were kindled until all of them showed the fifth stage of seizure for three consecutive times. Forty-eight hours after the last injection of pentylenetetrazole, 5 different doses of clozapine were administrated in separate studies and the results were compared with previous recorded seizure parameters obtained from the same animals using One-way ANOVA and paired t-test. The results showed that clozapine (1 mg/kg) has a proconvulsive effect, whereas in higher dose (7.5 mg/kg) it has an anticonvulsive effect on seizure parameters. Different doses of clozapine have different effects on seizure parameters and the discrepancy seen in human and animal reports may be due to the use of different doses of clozapine on pentylenetetrazole-induced kindling.