Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: Implications in addiction
Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: Implications in addiction
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DOI：
10.1176/ajp.156.1.19
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发表时间：
1999-01-01
影响因子：
17.7
通讯作者：
Pappas, N
中科院分区：
文献类型：
--
作者：
Volkow, ND;Wang, GJ;Pappas, N
目的：作者已经表明，可卡因滥用者多巴胺D-2受体的减少与扣带、前额叶和眶额叶皮质的代谢减少有关。为了评估增加多巴胺是否会逆转这些代谢下降，他们测量了哌甲酯（一种增加多巴胺的药物）对20名可卡因滥用者大脑葡萄糖代谢的影响。方法：受试者接受了两次[F-18]氟脱氧葡萄糖正电子发射断层扫描，一次是在连续两次安慰剂注射后，另一次是在两次哌甲酯静脉注射后。用[C-11]雷氯必利测定D2受体，以评价其与哌甲酯诱导的代谢变化的关系。结果如下：哌醋甲酯诱导脑代谢的变化：具有较高D2测量值的受试者倾向于增加代谢，而具有较低D2测量值的受试者倾向于降低代谢。哌醋甲酯对上级扣带回、右侧丘脑和小脑代谢增加的影响显著。哌醋甲酯引起的右眶额皮层和右纹状体的变化与渴望有关，而前额叶皮层的变化与情绪有关。结论：虽然哌醋甲酯增加了上级扣带回的代谢，但它只增加了分别增强渴望和情绪的受试者的眶额或前额皮质的代谢。这表明多巴胺增强本身不足以增加这些额叶区域的代谢。在报告渴望的受试者中，右眶额皮质和右纹状体（发现在强迫症中异常的脑区）的激活可能是成瘾者中强迫性药物给药的潜在机制之一。渴望与右脑区域而不是左脑区域的主要相关性表明了强化和/或条件反应的偏侧性。
Objective: The authors have shown that decreases in dopamine D-2 receptors in cocaine abusers were associated with decreased metabolism in the cingulate and prefrontal and orbitofrontal cortices. To assess whether increasing dopamine would reverse these metabolic decrements, they measured the effects of methylphenidate, a drug that increases dopamine, on brain glucose metabolism in 20 cocaine abusers. Method: The subjects underwent two [F-18]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [C-11]raclopride to evaluate their relation to methylphenidate-induced metabolic changes. Results: Methylphenidate induced variable changes in brain metabolism: subjects with the higher D2 measures tended to increase metabolism, whereas those with the lower D2 measures tended to decrease metabolism. Methylphenidate's effects were significant for increases in metabolism in the superior cingulate, right thalamus, and cerebellum. Methylphenidate-induced changes in the right orbitofrontal cortex and right striatum were associated with craving, and those in the prefrontal cortex were associated with mood. Conclusions: Although methylphenidate increased metabolism in the superior cingulate, it only increased metabolism in orbitofrontal or prefrontal cortices in the subjects in whom it enhanced craving and mood, respectively. This indicates that dopamine enhancement is not sufficient per se to increase metabolism in these frontal regions. Activation of the right orbitofrontal cortex and right striatum (brain regions found to be abnormal in compulsive disorders) in the subjects reporting craving may be one of the mechanisms underlying compulsive drug administration in addicted persons. The predominant correlation of craving with right but not left brain regions suggests laterality of reinforcing and/or conditioned responses.