title: The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity.
abstract: Lorcaserin (Lorqess, Belviq(®)) is a selective 5-HT(2C) receptor agonist that has received FDA approval for the treatment of obesity. 5-HT(2C) receptor agonists are also efficacious in decreasing multiple aspects of cocaine motivation and reward in preclinical models. This would suggest that lorcaserin is a clinically available therapeutic with the potential to treat cocaine addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin dose-dependently decreases cocaine self-administration on progressive and fixed ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of cocaine-seeking behaviour in response to priming injections of cocaine and/or reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently decreases cocaine-induced hyperlocomotion. Our results, when considered in concert with similar emergent findings in non-human primates, strongly support continued research into the potential of lorcaserin as a clinical treatment for cocaine addiction.
authors.affiliation: Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada. Electronic address: colin.harvey-lewis@camh.ca.
authors.forename: Colin
authors.initials: C
authors.lastname: Harvey-Lewis
authors.affiliation: Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Li
authors.affiliation: InterVivo Solutions Inc., 120 Carlton St., Toronto, ON, M5A 4K2, Canada; Dept. Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Higgins
authors.affiliation: Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada; Dept. of Psychiatry, University of Toronto, Toronto, ON, Canada; Dept. of Psychology, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000941:ethics; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D018490:Serotonin Agents / Q000494:pharmacology*
chemical_list: D001552:Benzazepines; D018765:Dopamine Uptake Inhibitors; D018490:Serotonin Agents; C506658:lorcaserin; D003042:Cocaine
keywords: 5-HT(2C) receptor; Cocaine; Locomotor activity; Lorcaserin; Reinstatement; Self-administration