title: Attenuation of apomorphine-induced sensitization by buspirone.
abstract: Apomorphine, a dopamine D₁/D₂ agonist is effective in the treatment of Parkinson's disease; but its long term use is often associated with the dependence and addiction. The development of locomotor sensitization to psychostimulants including apomorphine is considered to be an important contributor to psychostimulant drug abuse. Previous studies have shown that long term administration of drugs of abuse increases the effectiveness of somatodendritic 5-hydroxytryptamine (5-HT)-1A receptors. Repeated administration of buspirone attenuates the effectiveness of somatodendritic 5-HT(1A) receptors. The present study was designed to test the hypothesis that coadministration of buspirone may attenuate apomorphine induced sensitization. Administration of apomorphine at a dose of 1.0, 2.0 & 4.0mg/kg increased motor activity in an activity box in a dose dependent manner. Locomotor enhancing effects of a low dose of apomorphine were augmented upon repeated administration suggesting drug-induced sensitization. The sensitization effects were significant in an activity box as well as in an open field. Coadministration of buspirone at a dose of 1.0mg/kg reversed apomorphine-induced sensitization. Repeated administration of buspirone at a dose of 2.0 mg/kg but not 1.0 mg/kg also elicited sensitization in motor behavior. It is suggested that buspirone may oppose the development of sensitization to apomorphine by decreasing the sensitivity of somatodendritic 5-HT(1A) receptors. Findings may help in extending therapeutics in Parkinson's disease.
authors.affiliation: Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi-75270, Pakistan. huma_biochemist@yahoo.com
authors.forename: Huma
authors.initials: H
authors.lastname: Ikram
authors.forename: Darakhshan Jabeen
authors.initials: DJ
authors.lastname: Haleem
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D002065:Buspirone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001058:Apomorphine; D002065:Buspirone