Volkow N D, Wang G J, Fowler J S, Hitzemann R, Angrist B, Gatley S J, Logan J, Ding Y S, Pappas N
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Am J Psychiatry. 1999 Jan;156(1):19-26. doi: 10.1176/ajp.156.1.19.
The authors have shown that decreases in dopamine D2 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.
The subjects underwent two [18F]fluorodeoxyglucose positron emission tomography scans, one after two sequential placebo injections and one after two intravenous doses of methylphenidate. D2 receptors were measured with [11C]raclopride to evaluate their relation to methylphenidate-induced metabolic changes.
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.
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.
作者已表明，可卡因滥用者中多巴胺D2受体的减少与扣带回、前额叶和眶额皮质的代谢降低有关。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名可卡因滥用者脑葡萄糖代谢的影响。
受试者接受了两次[18F]氟脱氧葡萄糖正电子发射断层扫描，一次在连续两次注射安慰剂后进行，另一次在静脉注射两次哌甲酯后进行。用[11C]雷氯必利测量D2受体，以评估它们与哌甲酯诱导的代谢变化的关系。
哌甲酯引起脑代谢的可变变化：D2测量值较高的受试者倾向于增加代谢，而D2测量值较低的受试者则倾向于降低代谢。哌甲酯对扣带上部、右丘脑和小脑代谢增加的影响显著。哌甲酯引起的右眶额皮质和右纹状体的变化与渴望有关，前额叶皮质的变化与情绪有关。
尽管哌甲酯增加了扣带上部的代谢，但它仅在分别增强渴望和情绪的受试者的眶额皮质或前额叶皮质中增加了代谢。这表明多巴胺增强本身不足以增加这些额叶区域的代谢。报告有渴望的受试者中右眶额皮质和右纹状体（在强迫症中发现异常的脑区）的激活可能是成瘾者强迫性药物使用的潜在机制之一。渴望与右脑而非左脑区域的主要相关性表明强化和/或条件反应的偏侧性。
