title: Inhibition of apomorphine-induced behavioral sensitization in rats pretreated with fluoxetine.
abstract: Despite a number of clinically useful effects, there is growing evidence that psychosis and impulse control disorders develop in patients on apomorphine therapy. Evidence suggests a critical role of serotonin-1A receptors in psychosis, drug abuse, and in the mechanism of action of the prototypical selective serotonin reuptake inhibitor fluoxetine. We investigated whether fluoxetine can prevent apomorphine-induced behavioral sensitization in a rat model of psychosis. Animals treated with fluoxetine (5 and 10 mg/kg) for 2 weeks were subsequently cotreated with apomorphine (1.0 mg/kg) for 7 days. A single injection of apomorphine increased motor activity, whereas repeated daily injections produced a progressive sensitization of motor behavior. The sensitization effects of apomorphine did not occur in fluoxetine-pretreated and subsequently cotreated animals. To further elucidate the mechanism involved in the inhibition of apomorphine sensitization in fluoxetine-treated animals, we found that apomorphine-induced motor behavior was much greater in repeated apomorphine-treated than repeated saline-treated animals. It was also greater in apomorphine and fluoxetine-cotreated animals, but not in animals pretreated and cotreated with fluoxetine. The mechanism involved in the inhibition of apomorphine sensitization in fluoxetine-pretreated animals is discussed. The findings introduce an innovative approach for extending the therapeutic use of apomorphine and classical psychostimulant drugs.
authors.affiliation: aNeuroscience Research Laboratory, Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences bDepartment of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Darakhshan J
authors.initials: DJ
authors.lastname: Haleem
authors.forename: Muhammad
authors.initials: M
authors.lastname: Farhan
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011605:Psychoses, Substance-Induced / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001058:Apomorphine; D018491:Dopamine Agonists; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors