PSYCHOSTIMULANT EFFECTS IN HUMANS WITH DOPAMINE LESIONS

在实验动物中的病变研究记录了 中脑边缘/中皮层多巴胺神经元位于腹侧被盖 在精神兴奋剂的强化和奖励特性方面， 也许是其他滥用药物。 为了测试这种“多巴胺 假设”的精神刺激奖励是有效的，在人类，我们检查 精神兴奋剂对正常人主观情绪评定的影响 个体和患有帕金森氏症多巴胺细胞病变的人 疾病 先前的解剖学研究表明，CA。60%的VTA神经元可能 在这些大脑中被耗尽，尽管对黑质的损害 多巴胺系统更强 情绪、心血管参数和 在口服安慰剂后进行运动功能评级 或哌醋甲酯。 证据减少 帕金森病受试者的反应包括显著的 哌醋甲酯诱导的视觉“良好”感觉等级降低 模拟规模，并在几个相关的趋势减少 与年龄、种族和性别匹配的对照组相比， 这些 研究结果支持多巴胺能理论的精神兴奋剂奖励/ 强化人类。 未来的工作将试图检测是否有其他个体 多巴胺系统损害由于其他病理共享钝化 哌甲酯反应性。 具有不同程度的 通过多巴胺转运蛋白密度的PET研究评估的损伤， 也被评价。

Lesions studies in experimental animals document important roles for mesolimbic/mesocortial dopamine neurons lying in the ventral tegmental area in the reinforcing and rewarding properties of psychostimulants, and perhaps of other drugs of abuse. To test whether this "dopamine hypothesis" of psychostimulant reward is valid in humans, we examined psychostimulant effects on subjective ratings of mood in normal individuals and those with the dopamine cell lesions of Parkinson's disease. Prior anatomic studies suggest that ca. 60% of VTA neurons may be depleted in these brains, although the damage to the substantia nigra dopamine systems is greater. Subjective rating scales of mood, cardiovascular parameters, and locomotor functional ratings were performed after oral doses of placebo or methylphenidate using standard methods. Evidence for reduced responses in the Parkinson's disease subjects included significant reductions in methylphenidate-induced "good" feeling ratings on visual analog scales, and trends toward reductions in several associated measures in comparison to age- race- and sex-matched controls. These findings support dopaminergic theories of psychostimulant reward/ reinforcement in humans. Future work will attempt to detect whether other individuals with dopamine system damage due to other pathologies share blunted methylphenidate responsiveness. Individuals with different levels of damage as assessed by PET studies of dopamine transporter density, will also be evaluated.