低多巴胺 D2/D3 受体可及性与甲基苯丙胺依赖者延迟奖励的陡峭折扣有关。
Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence.
机构信息
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles (Drs Ballard, Ishibashi, Dean, and London); Department of Molecular and Medical Pharmacology, University of California Los Angeles (Robertson and Dr London); Brain Research Institute, University of California Los Angeles (Dr London); Veterans Affairs Greater Los Angeles Healthcare System, CA (Drs Ballard, Mandelkern, Ishibashi, and London and Robertson); Department of Physics, University of California Irvine, CA (Dr Mandelkern); Department of Psychology, University of Southern California, Los Angeles, CA (Dr Monterosso and Hsu).
出版信息
Int J Neuropsychopharmacol. 2015 Jan 20;18(7):pyu119. doi: 10.1093/ijnp/pyu119.
BACKGROUND
Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence.
METHODS
Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [(18)F]fallypride.
RESULTS
MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D2/D3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5).
CONCLUSIONS
These results provide the first direct evidence of a link between deficient D2/D3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed.
背景
物质使用障碍个体通常表现出即时满足的偏好，明显不顾及自己行为的未来后果。间接证据表明，纹状体中多巴胺 D2 型受体的可用性降低，导致这些个体倾向于牺牲长期目标来换取短期收益；然而，这种可能性尚未得到直接验证。我们研究了纹状体 D2/D3 受体的可用性是否与满足 DSM-IV 物质使用障碍标准的研究参与者对较小、更即时奖励的偏好呈负相关，而不是对较大、延迟的替代物的偏好。
方法
54 名成年人（n = 27 人：MA 依赖者，非使用者对照）完成了 Kirby 货币选择问卷，并进行了 [(18)F]fallypride 正电子发射断层扫描。
结果
MA 使用者表现出更陡峭的时间折扣（p = 0.030）和更低的纹状体 D2/D3 受体可用性（p < 0.0005），比对照组更低。折扣率与纹状体 D2/D3 受体可用性呈负相关，在合并样本中达到统计学意义（r = -0.291，p = 0.016）和 MA 使用者中（r = -0.342，p = 0.041），但在对照组中不显著（r = -0.179，p = 0.185）；MA 使用者和对照组之间的斜率没有显著差异（p = 0.5）。
结论
这些结果首次提供了 D2/D3 受体可用性不足与陡峭时间折扣之间联系的直接证据。这一发现与纹状体 D2/D3 受体可用性降低与兴奋剂使用者更高的复发风险有关的报告相符，可能有助于解释为什么一些个体尽管知道最终会产生负面后果，但仍选择继续使用毒品。讨论了未来的研究方向和治疗意义。
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