Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D(2) receptors.
Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D(2) receptors.
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发表时间：
1999-10
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通讯作者：
N. Volkow;N. Volkow;Gene-Jack Wang;J. Fowler;J. Logan;S. Gatley;C. Wong;R. Hitzemann;N. Pappas
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作者：
N. Volkow;N. Volkow;Gene-Jack Wang;J. Fowler;J. Logan;S. Gatley;C. Wong;R. Hitzemann;N. Pappas
边缘脑区多巴胺浓度的增加被认为是精神刺激剂对实验动物的增强作用的基础。然而，在人类中，药物引起的大脑多巴胺增加与精神刺激药物的增强作用之间的定性或定量关系尚未得到研究。用正电子发射断层扫描仪和与内源性多巴胺竞争D(2)受体的放射性配基[(11)C]拉氯普利测定不同剂量静脉注射后脑多巴胺的变化。14例健康对照的哌甲酸甲酯。同时，获得了药物效果自我报告的指标，以评估它们与哌醋甲酯诱导的脑多巴胺变化的关系。哌醋甲酯引起的“兴奋”强度与释放的多巴胺水平显著相关(r=0.78，p<；.001)；那些感觉到最强烈兴奋的受试者增加得最多。在排除了血浆中哌醋甲酯的剂量和浓度后，这种关系仍然显著。此外，没有增加多巴胺的受试者并没有感觉到兴奋。这些结果首次清楚地表明，兴奋剂诱导的兴奋--一种反映药物对人类强化效果的情绪描述符--与大脑中多巴胺的增加有关，而且多巴胺占用D(2)受体的水平与兴奋的强度之间存在定量关系。
Increases in dopamine concentration in limbic brain regions have been postulated to underlie the reinforcing effects of psychostimulant drugs in laboratory animals. However, neither the qualitative nor the quantitative relationship between drug-induced increases in brain dopamine and the reinforcing effects of psychostimulant drugs have been investigated in humans. Positron emission tomograph and [(11)C]raclopride, a dopamine D(2) receptor radioligand that competes with endogenous dopamine for occupancy of the D(2) receptors, were used to measure changes in brain dopamine after different doses of i.v. methylphenidate in 14 healthy controls. In parallel, measures for self-reports of drug effects were obtained to assess their relationship to methylphenidate-induced changes in brain dopamine. The intensity of the "high" induced by methylphenidate was significantly correlated with the levels of released dopamine (r = 0.78, p <.001); subjects having the greatest increases were those who perceived the most intense high. This relationship remained significant after partialing out for dose and concentration of methylphenidate in plasma. Furthermore, subjects for whom methylphenidate did not increase dopamine did not perceive a high. These results represent the first clear demonstration that stimulant-induced high, a mood descriptor that reflects reinforcing effects of drugs in humans, is associated with increases in brain dopamine, and also that there is a quantitative relationship between levels of D(2) receptor occupancy by dopamine and the intensity of the high.