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Inhibition of apomorphine-induced behavioral sensitization in rats pretreated with fluoxetine

Haleem, Darakhshan J.; Farhan, Muhammad

doi: 10.1097/FBP.0000000000000040
Research Reports

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.

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

Correspondence to Darakhshan J. Haleem, PhD, 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 E-mails: darakhshan-haleem@yahoo.com, djhaleem@uok.edu.pk

Received August 28, 2013

Accepted March 14, 2014

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