†InterVivo Solutions Inc., 120 Carlton Street, Toronto, ON M5A 4K2, Canada.
§Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada.
ACS Chem Neurosci. 2015 Jul 15;6(7):1071-88. doi: 10.1021/acschemneuro.5b00025. Epub 2015 Apr 14.
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.
神经递质 5-羟色胺（5-HT；血清素）长期以来一直与各种动机行为的控制有关，包括进食。将 5-HT 与进食行为联系起来的大部分证据来自于研究 5-HT 释放剂（dex）芬氟拉明在实验室动物和人类中的作用。最近，选择性 5-HT2C 受体激动剂lorcaserin 获得 FDA 批准用于治疗肥胖症。这篇综述检查了支持使用选择性 5-HT2C 受体激动剂治疗肥胖症以外的疾病的证据，包括物质滥用（特别是尼古丁、精神兴奋剂和酒精依赖）、强迫症和过度赌博障碍。简要回顾了支持 5-HT 调节食物和药物强化作用的早期文献后，我们提出，SSRIs 和 5-HT 释放剂之间的内在差异可能低估了基于 5-HT 的药物治疗治疗肥胖症以外的临床形式成瘾行为的价值。然后，我们强调了 5-HT2C 受体在介导（dex）芬氟拉明对进食和体重增加的影响中的关键作用，以及 5-HT2C 受体激动剂降低药物奖励和冲动性的证据。最近 lorcaserin 在戒烟试验中的疗效报告进一步加强了这样一种观点，即 5-HT2C 受体激动剂可能具有作为治疗成瘾的潜力。这篇综述是为 2014 年 7 月 9 日至 12 日在南非赫曼努斯举行的第 11 届国际血清素研究学会会议的会议记录而撰写的。
