Inserm U862, Neurocentre Magendie, Physiopathology of Addiction Group, Bordeaux, France.
Exp Brain Res. 2013 Oct;230(4):537-45. doi: 10.1007/s00221-013-3593-2. Epub 2013 Jun 8.
This review provides an overview of the role of central serotonin2C (5-HT2C) receptors in drug addiction, specifically focusing on their impact on the neurochemical and behavioral effects of cocaine, one of the most worldwide abused drug. First, we described the neurochemical and electrophysiological mechanisms underlying the interaction between 5-HT2C receptors and the mesocorticolimbic dopaminergic network, in keeping with the key role of this system in drug abuse and dependence. Thereafter, we focused on the role of 5-HT2C receptors in the effects of cocaine in various preclinical behavioral models used in drug addiction research, such as locomotor hyperactivity, locomotor sensitization, drug discrimination, and self-administration, to end with an overview of the neurochemical mechanisms underlying the interactions between 5-HT2C receptors, mesocorticolimbic dopamine system, and cocaine. On their whole, the presented data provide compelling preclinical evidence that 5-HT2C receptor agonists may have efficacy in the treatment of cocaine abuse and dependence, thereby underlying the need for additional clinical studies to ascertain whether preclinical data translate to the human.
这篇综述概述了中枢 5-羟色胺 2C(5-HT2C)受体在药物成瘾中的作用,特别是集中讨论了它们对可卡因(一种全球滥用最广泛的毒品)的神经化学和行为效应的影响。首先,我们描述了 5-HT2C 受体与中脑边缘多巴胺能网络相互作用的神经化学和电生理机制,这与该系统在药物滥用和依赖中的关键作用相一致。此后,我们重点介绍了 5-HT2C 受体在可卡因在各种用于药物成瘾研究的临床前行为模型中的作用,如运动过度兴奋、运动敏化、药物辨别和自我给药,最后概述了 5-HT2C 受体、中脑边缘多巴胺系统和可卡因之间相互作用的神经化学机制。总的来说,这些数据提供了令人信服的临床前证据,表明 5-HT2C 受体激动剂可能对治疗可卡因滥用和依赖有效,因此需要进一步的临床研究来确定临床前数据是否适用于人类。