Nonkes Lourens J P, van Bussel Inge P G, Verheij Michel M M, Homberg Judith R
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Behav Pharmacol. 2011 Dec;22(8):723-38. doi: 10.1097/FBP.0b013e32834d6260.
Cocaine addiction is a major health problem that affects millions of people. Cocaine acts by inhibiting dopamine, noradrenaline and serotonin [5-hydroxytryptamine(5-HT)] reuptake. The dopaminergic system is generally assumed to be involved in the reinforcing aspects of the drug, but the role of 5-HT in the addictive potential of cocaine is unclear. In light of pharmacological manipulations and cocaine use-related disease states affecting brain 5-HT levels, we review studies on the effect of cocaine on central 5-HT function. In addition, the contribution of 5-HT to the rewarding, aversive, discriminative and subjective, as well as the motivational and reinforcing effects of cocaine is discussed. We specifically focus on net changes in the extracellular 5-HT levels that occur as a consequence of acute and chronic cocaine exposure and how these influence cocaine abuse-related behaviour. Overall, the data indicate that 5-HT plays a major role in the psychomotor stimulant, rewarding and discriminative stimulant effects of cocaine, but also affects the motivational and reinforcing effects of the drug. In addition, 5-HT mediates, to some extent, the aversive effects of cocaine. Difficulties with data interpretation are discussed.
可卡因成瘾是一个影响数百万人的重大健康问题。可卡因通过抑制多巴胺、去甲肾上腺素和5-羟色胺（5-HT）的再摄取发挥作用。一般认为多巴胺能系统与该药物的强化作用有关，但5-HT在可卡因成瘾潜力中的作用尚不清楚。鉴于影响脑5-HT水平的药理学操作及与可卡因使用相关的疾病状态，我们综述了关于可卡因对中枢5-HT功能影响的研究。此外，还讨论了5-HT对可卡因的奖赏、厌恶、辨别和主观效应，以及动机和强化效应的作用。我们特别关注急性和慢性可卡因暴露导致的细胞外5-HT水平的净变化，以及这些变化如何影响与可卡因滥用相关的行为。总体而言，数据表明5-HT在可卡因的精神运动兴奋、奖赏和辨别兴奋效应中起主要作用，但也会影响该药物的动机和强化效应。此外，5-HT在一定程度上介导了可卡因的厌恶效应。文中还讨论了数据解释方面的困难。
