ACUTE AND CHRONIC ADMINISTRATION OF CLOZAPINE PRODUCES GREATER PROCONVULSANT ACTIONS THAN HALOPERIDOL ON FOCAL HIPPOCAMPAL SEIZURES IN FREELY MOVING RATS

In this study, we assessed the effects of the acute (a single injectio n) and repeated (once daily injections for 21 days) administration of the atypical antipsychotic drug clozapine (1.5, 5, or 15 mg/kg i.p.) a nd the typical antipsychotic drug haloperidol (0.15, 0.5, and 1.5 mg/k g, i.p.) on hippocampal partial seizures generated by low-frequency el ectrical stimulation in male Wistar rats. The seizure threshold and se verity were determined by measuring the pulse number threshold (PNT) a nd the primary afterdischarge duration (ADD), respectively. A single i njection of either 5 or 15 mg/kg of clozapine significantly decreased the PNT and significantly increased the primary ADD, indicating a proc onvulsant action. The repeated administration of clozapine (1.5, 5, or 15 mg/kg, i.p.) produced dose-dependent, proconvulsant effects by sig nificantly decreasing the PNT and by significantly increasing the prim ary ADD. In contrast to clozapine, the acute administration of haloper idol did not significantly alter the PNT or the primary ADD. The repea ted administration of haloperidol (0.5 and 1.5 mg/kg, i.p.), unlike cl ozapine, significantly decreased the primary ADD, but did not alter th e PNT. Overall, clozapine produces a greater proconvulsant action than haloperidol in an animal model of hippocampal seizures. (C) 1998 Wile y-Liss, Inc.