Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence.
Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence.
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DOI：
10.1093/ijnp/pyu119
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发表时间：
2015-01-20
期刊：
影响因子：
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通讯作者：
London ED
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文献类型：
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作者：
Ballard ME;Mandelkern MA;Monterosso JR;Hsu E;Robertson CL;Ishibashi K;Dean AC;London ED
患有物质使用障碍的人通常表现出对即时满足的偏好，显然忽视了他们行为的未来后果。间接证据表明，纹状体中多巴胺D2型受体的低可获得性有助于这些个体为了短期收益而牺牲长期目标的倾向；然而，这种可能性尚未得到直接测试。我们调查了在符合DSM-IV甲基苯丙胺(MA)依赖标准的研究参与者中，纹状体D2/D3受体的可用性是否与偏好较小的、更直接的奖励而不是较大的、延迟的替代方案呈负相关。54名成年人(n=27：MA依赖、非用户对照)完成了Kirby货币选择问卷，并接受了[18F]FolyPride的正电子发射断层扫描。与对照组相比，MA患者显示出更陡峭的时间折扣率(p=0.030)和更低的纹状体D2/D3受体可用性(p<；0.0005)。贴现率与纹状体D2/D3受体的可用性呈负相关，在联合样本(r=-0.291，p=0.016)和单独使用MA的患者之间(r=-0.342，p=0.041)达到统计学意义，但在单独的对照中(r=-0.179，p=0.185)，斜率在MA用户和对照组之间没有显著差异(p=0.50)。这些结果首次直接证明了D2/D3受体活性不足与时间折扣过大之间的联系。这一发现与纹状体D2/D3受体可用性低与兴奋剂使用者复发风险较高有关的报道相吻合，并可能有助于解释为什么一些人在知道药物最终的负面后果的情况下仍选择继续使用药物。并讨论了今后的研究方向和治疗意义。
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. Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [18F]fallypride. 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). 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.