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: Darakhshan J Haleem, Muhammad Farhan
• Journal: Behavioural pharmacology (Behav Pharmacol) Vol. 26 Issue 1-2 Pg. 159-66 (Feb 2015) ISSN: 1473-5849 [Electronic] England
• PMID: 24755891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Agonists
• Serotonin Uptake Inhibitors
• Fluoxetine
• Apomorphine

Topics

• Animals
• Apomorphine (administration & dosage, pharmacology, toxicity)
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Dopamine Agonists (administration & dosage, pharmacology, toxicity)
• Dose-Response Relationship, Drug
• Fluoxetine (administration & dosage, pharmacology)
• Male
• Motor Activity (drug effects)
• Psychoses, Substance-Induced (etiology, physiopathology, prevention & control)
• Rats
• Rats, Wistar
• Selective Serotonin Reuptake Inhibitors (administration & dosage, pharmacology)