Amphetamine-induced dopamine release: Markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine
Amphetamine-induced dopamine release: Markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine
复制标题
DOI：
10.1176/appi.ajp.164.4.622
复制
发表时间：
2007-04-01
影响因子：
17.7
通讯作者：
Laruelle, Marc
中科院分区：
文献类型：
--
作者：
Martinez, Diana;Narendran, Rajesh;Laruelle, Marc
目的：多巴胺是可卡因强化效应的重要调节因子，多巴胺功能的改变可能与可卡因依赖有关。本研究的目的是表征最近解毒可卡因依赖受试者突触前和突触后多巴胺功能。具体来说，使用正电子发射断层扫描（PET）评估了可卡因依赖者和健康对照者纹状体亚区对急性安非他明刺激的多巴胺反应。此外，这种多巴胺反应和选择自我服用可卡因在实验室模型的复发之间的关系进行了调查。方法：24名可卡因依赖者和24名匹配的健康受试者在基线条件下和静脉注射安非他明（0.3 mg/ kg）后接受[C-11]雷氯pride扫描。依赖可卡因的参与者还完成了可卡因自我给药的环节，在这个环节中，在可卡因启动剂量之后，他们选择是自我给药，还是获得金钱奖励。结果：可卡因依赖与纹状体各功能亚区安非他明诱导的多巴胺释放显著减少有关（可卡因依赖参与者的边缘纹状体：-1.2%，而健康受试者为-12.4%；联想纹状体：-2.6%，而健康受试者为-6.7%；感觉运动纹状体：-4.3%，而健康受试者为-14.1%）。在腹侧纹状体和前尾状体中，多巴胺传递减弱预示着可卡因比金钱更容易被选择。结论：可卡因依赖与多巴胺功能损害有关，这种损害似乎在复发中起关键作用。
Objective: Dopamine is an important mediator of the reinforcing effects of cocaine, and alterations in dopamine function might be involved in cocaine dependence. The goals of the present study were to characterize pre- and postsynaptic dopamine function in recently detoxified cocaine-dependent subjects. Specifically, dopamine response to an acute amphetamine challenge was assessed in striatal subregions in cocaine-dependent and healthy comparison participants using positron emission tomography (PET). Furthermore, the relationship between this dopamine response and the choice to self-administer cocaine in a laboratory model of relapse was investigated.Method: Twenty-four cocaine-dependent participants and 24 matched healthy subjects underwent [C-11] raclopride scans under a baseline condition and following intravenous amphetamine administration (0.3 mg/ kg). Cocaine-dependent participants also completed cocaine self-administration sessions in which a priming dose of cocaine was followed by the choice to either self-administer subsequent cocaine doses or receive a monetary reward.Results: Cocaine dependence was associated with a marked reduction in amphetamine-induced dopamine release in each of the functional subregions of the striatum (limbic striatum: -1.2% in cocaine-dependent participants versus -12.4% in healthy subjects; associative striatum: -2.6% versus -6.7%, respectively; sensorimotor striatum: -4.3% versus -14.1%). Blunted dopamine transmission in the ventral striatum and anterior caudate was predictive of the choice for cocaine over money.Conclusions: Cocaine dependence is associated with impairment of dopamine function, and this impairment appears to play a critical role in relapse.