Harvey-Lewis Colin, Li Zhaoxia, Higgins Guy A, Fletcher Paul J
Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada.
Section of Biopsychology and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada.
Neuropharmacology. 2016 Feb;101:237-45. doi: 10.1016/j.neuropharm.2015.09.028. Epub 2015 Sep 30.
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.
氯卡色林(Lorqess,Belviq®)是一种选择性5-羟色胺(5-HT)2C受体激动剂,已获得美国食品药品监督管理局(FDA)批准用于治疗肥胖症。在临床前模型中,5-HT2C受体激动剂在降低可卡因动机和奖赏的多个方面也有效果。这表明氯卡色林是一种临床上可用的、有潜力治疗可卡因成瘾的疗法。在此,我们报告氯卡色林(0.1毫克/千克 - 1.0毫克/千克)对大鼠可卡因相关行为多个方面的影响。我们发现,氯卡色林在递增和固定比率强化程序上剂量依赖性地减少可卡因自我给药。氯卡色林还能减少因可卡因引发注射和/或重新引入可卡因相关线索而导致的可卡因觅药行为恢复。最后,氯卡色林剂量依赖性地减少可卡因诱导的运动亢进。我们的结果与在非人灵长类动物中类似的新发现一致,有力地支持继续研究氯卡色林作为可卡因成瘾临床治疗方法的潜力。