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 i s 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.
Health Public Relevance Statement Health problems related to drug abuse/dependence have recently been estimated to cost over pound 12 billion annually in the UK (Godfrey et al, 2002) and over $ 180 billion annually in the USA (Anon, 2004). Although there do exist a variety of drug treatments to assist recovery in drug addicts, in particular for treating drug craving (O'Brien, 2005), relapse rates are high (McLellan, 2000). There remains therefore a pressing need for effective treatments of drug abuse/dependence.
|Gerak, Lisa R; Collins, Gregory T; France, Charles P (2016) Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys. J Pharmacol Exp Ther 359:383-391|
|Collins, Gregory T; Gerak, Lisa R; Javors, Martin A et al. (2016) Lorcaserin Reduces the Discriminative Stimulus and Reinforcing Effects of Cocaine in Rhesus Monkeys. J Pharmacol Exp Ther 356:85-95|