PSYCHOSTIMULANT EFFECTS IN HUMANS WITH DOPAMINE LESIONS

多巴胺损伤人类的精神兴奋作用

• 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
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3775007
• 关键词: Parkinson's disease; cardiovascular function; central nervous system stimulants; chemical stimulation; dopamine; emotions; functional ability; human subject; methylphenidate; neural degeneration; neuropharmacology; psychopharmacology; reinforcer

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.

实验动物的病变研究证明了