title: The Serotonin 2C Receptor Agonist Lorcaserin Attenuates Intracranial Self-Stimulation and Blocks the Reward-Enhancing Effects of Nicotine.
abstract: Lorcaserin, a serotonin (5-hydroxytryptamine, 5-HT) 2C receptor agonist, was recently approved for the treatment of obesity. We previously suggested that 5-HT2C receptor agonists affect reward processes and reduce the rewarding effects of drugs of abuse. Here, we determined whether lorcaserin (1) decreases responding for brain stimulation reward (BSR) and (2) prevents nicotine from enhancing the efficacy of BSR. Rats were trained on the intracranial self-stimulation (ICSS) paradigm to nosepoke for BSR of either the dorsal raphé nucleus or left medial forebrain bundle. In Experiment 1, lorcaserin (0.3-1.0 mg/kg) dose-dependently reduced the efficacy of BSR. This effect was blocked by prior administration of the 5-HT2C receptor antagonist SB242084. In Experiment 2, separate groups of rats received saline or nicotine (0.4 mg/kg) for eight sessions prior to testing. Although thresholds were unaltered in saline-treated rats, nicotine reduced reward thresholds. An injection of lorcaserin (0.3 mg/kg) prior to nicotine prevented the reward-enhancing effect of nicotine across multiple test sessions. These results demonstrated that lorcaserin reduces the rewarding value of BSR and also prevents nicotine from facilitating ICSS. Hence, lorcaserin may be effective in treating psychiatric disorders, including obesity and nicotine addiction, by reducing the value of food or drug rewards.
authors.affiliation: †Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada.
authors.forename: Fiona D
authors.initials: FD
authors.lastname: Zeeb
authors.affiliation: ‡InterVivo Solutions Inc., Toronto, Ontario L5N 8G4, Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Higgins
authors.affiliation: †Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D020318:Rats, Long-Evans; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects* / Q000502:physiology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D001552:Benzazepines; D007211:Indoles; D018722:Nicotinic Agonists; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C506658:lorcaserin; D009538:Nicotine
keywords: Brain stimulation reward; intracranial self-stimulation; lorcaserin; nicotine; reward; serotonin 2C receptor