title: Reversal of haloperidol-induced extrapyramidal symptoms by buspirone: a time-related study.
abstract: 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.
authors.affiliation: Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi, Pakistan. darakhshan_haleem@yahoo.com
authors.forename: Darakhshan Jabeen
authors.initials: DJ
authors.lastname: Haleem
authors.forename: Noreen
authors.initials: N
authors.lastname: Samad
authors.forename: Muhammad Abdul
authors.initials: MA
authors.lastname: Haleem
mesh_terms: 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
chemical_list: D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D006220:Haloperidol; D002065:Buspirone