Martinez Diana, Narendran Rajesh, Foltin Richard W, Slifstein Mark, Hwang Dah-Ren, Broft Allegra, Huang Yiyun, Cooper Thomas B, Fischman Marian W, Kleber Herbert D, Laruelle Marc
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Am J Psychiatry. 2007 Apr;164(4):622-9. doi: 10.1176/ajp.2007.164.4.622.
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.
Twenty-four cocaine-dependent participants and 24 matched healthy subjects underwent [(11)C]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.
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.
Cocaine dependence is associated with impairment of dopamine function, and this impairment appears to play a critical role in relapse.
多巴胺是可卡因强化作用的重要介质，多巴胺功能的改变可能与可卡因依赖有关。本研究的目的是描述近期戒毒的可卡因依赖者突触前和突触后多巴胺功能的特征。具体而言，使用正电子发射断层扫描（PET）评估可卡因依赖者和健康对照参与者纹状体亚区域对急性苯丙胺激发的多巴胺反应。此外，还研究了这种多巴胺反应与在复发实验室模型中自我给药可卡因选择之间的关系。
24名可卡因依赖参与者和24名匹配的健康受试者在基线条件下和静脉注射苯丙胺（0.3mg/kg）后接受[（11）C]雷氯必利扫描。可卡因依赖参与者还完成了可卡因自我给药环节，在给予一剂可卡因起始剂量后，他们可以选择自我给药后续剂量的可卡因或获得金钱奖励。
可卡因依赖与纹状体每个功能亚区域中苯丙胺诱导的多巴胺释放显著减少有关（边缘纹状体：可卡因依赖参与者为-1.2%，健康受试者为-12.4%；联合纹状体：分别为-2.6%和-6.7%；感觉运动纹状体：-4.3%和-14.1%）。腹侧纹状体和前尾状核中多巴胺传递减弱预示着选择可卡因而非金钱。
可卡因依赖与多巴胺功能受损有关，这种损害似乎在复发中起关键作用。
