Instituto de Drogas y Conductas Adictivas, Universidad CEU Cardenal Herrera, Avda. Seminario s/n 46113 Moncada, Valencia, Spain.
Synapse. 2010 May;64(5):397-402. doi: 10.1002/syn.20741.
Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [(11)C]raclopride and positron emission tomography and response to monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.
先前的研究报告显示,在成瘾个体中,静息状态下多巴胺(DA)D2 受体的可用性水平较低,与腹侧和背侧前额叶代谢减少有关。DA D2 受体可用性的减少以及腹侧前额叶代谢的减少被认为是对非药物奖励敏感性降低的基础,这是非药物成瘾的核心特征。因此,我们假设在基线时 DA D2 受体可用性的变异性将与成瘾个体对货币奖励的动态反应相关。通过 [(11)C]raclopride 和正电子发射断层扫描测量纹状体 DA D2 受体的可用性,并在七名可卡因成瘾个体中(平均三年后)使用功能磁共振成像测量对货币奖励的反应。结果表明,背侧纹状体中 DA D2 受体的低可用性与对货币奖励的丘脑反应降低有关;而腹侧纹状体的低可用性与对货币奖励的内侧前额叶(Brodmann 区域 6/8/32)反应增加有关。这些初步结果需要在更大的样本量中进行复制,并通过健康对照组进行验证,表明静息状态下纹状体 DA D2 受体的可用性可预测可卡因成瘾个体对非药物强化剂(金钱)的前额叶皮层功能反应的变异性,这与行为监测有关,而与条件反应和预期有关的丘脑也与行为监测有关。