title: Therapeutic Potential of 5-HT2C Receptor Agonists for Addictive Disorders.
abstract: The neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) has long been associated with the control of a variety of motivated behaviors, including feeding. Much of the evidence linking 5-HT and feeding behavior was obtained from studies of the effects of the 5-HT releaser (dex)fenfluramine in laboratory animals and humans. Recently, the selective 5-HT2C receptor agonist lorcaserin received FDA approval for the treatment of obesity. This review examines evidence to support the use of selective 5-HT2C receptor agonists as treatments for conditions beyond obesity, including substance abuse (particularly nicotine, psychostimulant, and alcohol dependence), obsessive compulsive, and excessive gambling disorder. Following a brief survey of the early literature supporting a role for 5-HT in modulating food and drug reinforcement, we propose that intrinsic differences between SSRI and serotonin releasers may have underestimated the value of serotonin-based pharmacotherapeutics to treat clinical forms of addictive behavior beyond obesity. We then highlight the critical involvement of the 5-HT2C receptor in mediating the effect of (dex)fenfluramine on feeding and body weight gain and the evidence that 5-HT2C receptor agonists reduce measures of drug reward and impulsivity. A recent report of lorcaserin efficacy in a smoking cessation trial further strengthens the idea that 5-HT2C receptor agonists may have potential as a treatment for addiction. This review was prepared as a contribution to the proceedings of the 11th International Society for Serotonin Research Meeting held in Hermanus, South Africa, July 9-12, 2014.
authors: †InterVivo Solutions Inc., 120 Carlton Street, Toronto, ON M5A 4K2, Canada.
authors: Guy A
authors: GA
authors: Higgins
authors: §Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada.
authors: Paul J
authors: PJ
authors: Fletcher
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016739:Behavior, Addictive / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D012701:Serotonin; D058826:Serotonin 5-HT2 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors
keywords: 5-HT2C receptor; Serotonin; addiction; impulsivity; lorcaserin; nicotine dependence; obesity