Evaluation of the 5-HT2C agonist lorcaserin as potential treatment for cocaine ab

University Of Texas Hlth Science Center, San Antonio TX

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Abstract

DESCRIPTION (provided by applicant): The positive reinforcing properties of drugs of abuse are thought to result from enhanced activity in meso-limbic dopamine (DA) systems. In addition to direct blockade of DA transmission by classical and atypical antipsychotics, an alternative approach to diminishing central DA activity is via stimulation of serotonin 5-HT2C receptors. The research described in the present proposal will evaluate one such 5-HT2C agonist lorcaserin, already well advanced in clinical development in other indications, for its attenuation of cocaine abuse-related behavior in the rhesus monkey. Data obtained in this non-human primate (NHP) should better predict clinical effects in humans than data from rodents. The aim is to determine whether the NHP data would provide encouragement, or not, for the clinical testing of lorcaserin for treating cocaine abuse in humans. The experiments will evaluate lorcaserin for attenuation of cocaine-induced hyperactivity; cocaine maintained self-administration behavior and the internal stimulus properties of cocaine in a drug discrimination procedure. To demonstrate that lorcaserin could be useful for treating cocaine abuse in humans, these experiments should show that lorcaserin is effective in attenuating cocaine abuse- related behavior in NHP at doses without intrinsic effects on behavior.