Acute and chronic administration of clozapine produces greater proconvulsant actions than haloperidol on focal hippocampal seizures in freely moving rats

• Published in: Synapse (New York, N.Y.) Vol. 29; no. 3; pp. 272 - 278
• Main Authors: Minabe, Yoshio, Watanabe, Kei-Ichiro, Nishimura, Tsutomu, Ashby Jr, Charles R.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.07.1998
• Subjects: Animals; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - pharmacology; clozapine; Clozapine - administration & dosage; Clozapine - pharmacology; epilepsy; haloperidol; Haloperidol - administration & dosage; Haloperidol - pharmacology; hippocampus; Hippocampus - physiopathology; Injections, Intraperitoneal; kindling; Kindling, Neurologic - physiology; Male; Rats; Rats, Wistar; Seizures - etiology; Seizures - physiopathology; Time Factors
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/(SICI)1098-2396(199807)29:3<272::AID-SYN10>3.0.CO;2-V

In this study, we assessed the effects of the acute (a single injection) and repeated (once daily injections for 21 days) administration of the atypical antipsychotic drug clozapine (1.5, 5, or 15 mg/kg i.p.) and the typical antipsychotic drug haloperidol (0.15, 0.5, and 1.5 mg/kg, i.p.) on hippocampal partial seizures generated by low‐frequency electrical stimulation in male Wistar rats. The seizure threshold and severity were determined by measuring the pulse number threshold (PNT) and the primary afterdischarge duration (ADD), respectively. A single injection of either 5 or 15 mg/kg of clozapine significantly decreased the PNT and significantly increased the primary ADD, indicating a proconvulsant action. The repeated administration of clozapine (1.5, 5, or 15 mg/kg, i.p.) produced dose‐dependent, proconvulsant effects by significantly decreasing the PNT and by significantly increasing the primary ADD. In contrast to clozapine, the acute administration of haloperidol did not significantly alter the PNT or the primary ADD. The repeated administration of haloperidol (0.5 and 1.5 mg/kg, i.p.), unlike clozapine, significantly decreased the primary ADD, but did not alter the PNT. Overall, clozapine produces a greater proconvulsant action than haloperidol in an animal model of hippocampal seizures. Synapse 29:272–278, 1998. © 1998 Wiley‐Liss, Inc.