Effects of methylphenidate on regional brain glucose metabolism in humans: relationship to dopamine D2 receptors.
Effects of methylphenidate on regional brain glucose metabolism in humans: relationship to dopamine D2 receptors.
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DOI：
10.1176/ajp.154.1.50
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
N. D. Volkow;Gene-Jack Wang;Joanna S. Fowler;J. Logan;Burton Angrist;R. Hitzemann;Jeffrey A. Lieberman;N. Pappas
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文献类型：
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作者：
N. D. Volkow;Gene-Jack Wang;Joanna S. Fowler;J. Logan;Burton Angrist;R. Hitzemann;Jeffrey A. Lieberman;N. Pappas
目的：作者的目标是确定基线多巴胺活性是否有助于哌醋甲酯的反应，并评估与多巴胺活性增强相关的代谢反应模式。方法他们使用2-脱氧-2 [18 F]氟-D-葡萄糖的正电子发射断层扫描来评估两个连续剂量的哌醋甲酯对15名健康受试者脑代谢的影响。多巴胺D2受体的可用性与[11 C]雷氯必利，以评估其与哌甲酯诱导的代谢变化的关系。结果哌醋甲酯在6名受试者中增加了脑代谢，在2名受试者中减少了脑代谢，在7名受试者中没有改变脑代谢;然而，哌醋甲酯持续增加小脑代谢。哌醋甲酯显著增加了小脑的“相对”（相对于整个大脑的区域）代谢，并降低了基底神经节的代谢。小脑、额叶和颞叶皮质的区域代谢变化与D2的可用性显著相关。额叶和颞叶代谢增加的受试者与高D2受体和降低受试者与低D2受体。结论哌醋甲酯引起脑代谢的变化，但它始终增加小脑代谢。它还诱导基底神经节中相对代谢的显著减少。额叶和颞叶皮质以及小脑和D2受体的代谢变化之间的显着关联表明，哌甲酯在这些脑区的代谢效应部分是由于多巴胺的变化，D2受体的差异可能是解释哌甲酯反应的可变性的机制之一。
OBJECTIVE The authors' goals were to determine whether baseline dopamine activity contributes to response to methylphenidate and to assess the pattern of metabolic responses associated with enhanced dopamine activity. METHOD They used positron emission tomography with 2-deoxy-2[18F]fluoro-D-glucose to evaluate the effects of two sequential doses of methylphenidate on brain metabolism in 15 healthy subjects. Dopamine D2 receptor availability was measured with [11C]raclopride to evaluate its relation to methylphenidate-induced metabolic changes. RESULTS Methylphenidate increased brain metabolism in six subjects, decreased it in two, and did not change it in seven; however, it consistently increased cerebellar metabolism. Methylphenidate significantly increased "relative" (region relative to the whole brain) metabolism in the cerebellum and decreased it in the basal ganglia. Regional metabolic changes in the cerebellum and the frontal and temporal cortices were significantly correlated with D2 availability. Frontal and temporal metabolism were increased in subjects with high D2 receptors and decreased in subjects with low D2 receptors. CONCLUSIONS Methylphenidate induced variable changes in brain metabolism, but it consistently increased cerebellar metabolism. It also induced a significant reduction in relative metabolism in the basal ganglia. The significant association between metabolic changes in the frontal and temporal cortices and in the cerebellum and D2 receptors suggests that methylphenidate's metabolic effects in these brain regions are due in part to dopamine changes and that differences in D2 receptors may be one of the mechanisms accounting for the variability in response to methylphenidate.