PSYCHOSTIMULANT EFFECTS IN HUMANS WITH DOPAMINE LESIONS

多巴胺损伤人类的精神兴奋作用

基本信息

批准号：
3775007
负责人：
G R UHL
金额：
--
依托单位：
NATIONAL INSTITUTE ON DRUG ABUSE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

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.

实验动物损伤研究记录了重要作用位于腹侧被盖的中边缘/中皮质多巴胺神经元精神兴奋剂的强化和奖励特性领域，以及也许是其他滥用药物。来测试一下这种“多巴胺精神刺激奖励的假设“在人类中是有效的，我们检查了精神刺激对正常人情绪主观评价的影响个人以及患有帕金森病多巴胺细胞病变的人疾病。先前的解剖学研究表明，大约。 60% 的 VTA 神经元可能尽管黑质受到损害，但这些大脑中的多巴胺系统更大。情绪、心血管参数的主观评分量表口服安慰剂后进行运动功能评级或哌醋甲酯使用标准方法。减少的证据帕金森病受试者的反应包括显着哌醋甲酯引起的视觉“良好”感觉评级降低模拟量表，以及几个相关的减少趋势与年龄、种族和性别匹配的对照进行比较的措施。这些研究结果支持精神兴奋剂奖励的多巴胺能理论/ 对人类的强化。未来的工作将尝试检测其他个体是否患有其他病理导致的多巴胺系统损伤减弱哌甲酯反应性。具有不同水平的个人通过多巴胺转运蛋白密度的 PET 研究评估的损伤将也进行评价。