title: Inhibition of apomorphine-induced conditioned place preference in rats co-injected with buspirone: relationship with serotonin and dopamine in the striatum.
abstract: Apomorphine is a non-narcotic derivative of morphine, which acts as a dopamine agonist to produce psychostimulant like effects. Currently, apomorphine is used in patients with advanced Parkinson׳s disease, for the treatment of persistent and disabling motor fluctuations, but a constellation of addictive syndromes such as excessive over use of medication, compulsive behaviors, and disturbances of impulse control are noticed in certain patients. Research on rodent models using conditioned place preference (CPP) paradigm also shows that the drug is rewarding. Previously we have shown that repeated administration of apomorphine produces behavioral sensitization which is prevented in rats co-injected with a low (1.0mg/kg) but not higher (2.0mg/kg) dose of buspirone. The present study shows that rewarding effects of apomorphine (1.0mg/kg) in a CPP paradigm are also blocked in rats co-injected with a low (1.0mg/kg) but not higher (2.0mg/kg) dose of buspirone. The levels of serotonin and its metabolite are decreased in the caudate as well as nucleus accumbens of rats exhibiting CPP and the decreases do not occur in animals co-injected with low or higher dose of buspirone. The levels of dopamine and its metabolites are not affected in animals exhibiting CPP; administration as well as co-administration of higher dose of buspirone decreased dopamine metabolism in the caudate as well as nucleus accumbens. The findings suggest a critical role of serotonin in the rewarding effects of apomorphine and imply that co-use of buspirone at low doses can help to control addictive syndromes in Parkinson׳s disease patients on apomorphine therapy.
authors.affiliation: Neuroscience Research Laboratory (Room No. 102), Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan. Electronic address: darakhshan-haleem@yahoo.com.
authors.forename: Darakhshan Jabeen
authors.initials: DJ
authors.lastname: Haleem
authors.affiliation: Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Huma
authors.initials: H
authors.lastname: Ikram
authors.affiliation: Department of Biomedical Engineering, Sir Syed University of Engineering and Technology, Karachi, Pakistan.
authors.forename: Muhammad Abdul
authors.initials: MA
authors.lastname: Haleem
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D018491:Dopamine Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D001058:Apomorphine; D002065:Buspirone; D004298:Dopamine
keywords: 5-HT-1A receptors; Apomorphine; Buspirone; Conditioned place preference (CPP) sensitization; Reward