Reversal of haloperidol-induced extrapyramidal symptoms by buspirone: a time-related study.
Effects of coadministration of buspirone were investigated on the time course of haloperidol-induced extrapyramidal symptoms in rats. Rats treated with haloperidol at a dose of 1 mg/kg exhibited impaired motor coordination and a decrease in exploratory activity. Coadministration of buspirone at a dose of 1 mg/kg attenuated haloperidol-induced deficits of motor coordination but no effect was produced on the deficits of exploratory activity, possibly because of a 'floor effect'. Long-term administration of haloperidol (1 mg/kg) twice a day for 5 weeks did not produce tolerance to haloperidol-induced deficits of exploratory activity. The deficits of motor coordination were attenuated after 4-5 weeks of drug administration. Coadministration of buspirone for 3-5 weeks attenuated and reversed haloperidol-induced deficits of exploratory activity. Deficits of motor coordination were smaller in rats cotreated with buspirone after 1 week but not after 2-5 weeks. Administration of haloperidol for 2 weeks elicited vacuous chewing movements with twitching of facial musculature that increased in a time-dependent manner as the treatment continued to 5 weeks. Animals cotreated with buspirone exhibited a gradual reversal of the response during 2-5 weeks of treatment. The mechanism involved in the attenuation/reversal of haloperidol-induced extrapyramidal symptoms by buspirone is discussed. Prior administration of buspirone for 2 weeks may be of help in the improvement of extrapyramidal symptoms induced by antipsychotic drugs.
Haleem
Darakhshan Jabeen
DJ
Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi, Pakistan. darakhshan_haleem@yahoo.com
Samad
Noreen
N
Haleem
Muhammad Abdul
MA
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001259:Ataxia / Q000139:chemically induced / Q000523:psychology; D002065:Buspirone / Q000627:therapeutic use*; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D006220:Haloperidol; D002065:Buspirone