Human Motor Control Section, National Institute on Neurological Disorders and Stroke, National Instutes of Health, Bethesda, Maryland.
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland.
Biol Psychiatry. 2019 Sep 1;86(5):356-364. doi: 10.1016/j.biopsych.2019.03.965. Epub 2019 Mar 15.
Preclinical and human positron emission tomography studies have produced inconsistent results regarding the effects of opioids on mesolimbic dopamine (DA). Here, we quantify striatal DA release (measured by [C]raclopride displacement) in response to an intravenous infusion of morphine, and its relationship with morphine-induced subjective effects, in healthy, nondependent opioid-experienced participants.
Fifteen healthy male participants were initially included. Sessions were on separate days. On session 1, participants received intravenous morphine (10 mg/70 kg) in the clinic to ensure tolerability. Participants without adverse reactions (n = 10) then received intravenous morphine and placebo (saline) sessions, in counterbalanced order, while undergoing [C]raclopride positron emission tomography scans. Subjective and physiological responses were assessed. Region-of-interest and voxelwise image analyses were used to assess changes in [C]raclopride nondisplaceable binding potential.
Morphine produced marked subjective and physiological effects and induced a significant decrease in [C]raclopride nondisplaceable binding potential, particularly in the nucleus accumbens and globus pallidus, where the change in [C]raclopride nondisplaceable binding potential was approximately 9%. However, the subjective effects of morphine did not show a simple pattern of correlation with DA release.
This is, to our knowledge, the first study providing in vivo human evidence that DA transmission in the ventral striatum is affected by morphine. Further studies are required to fully delineate the DA contribution to the reinforcing effects of opioids.
临床前和人体正电子发射断层扫描研究对于阿片类药物对中脑边缘多巴胺（DA）的影响产生了不一致的结果。在这里，我们定量测量了纹状体 DA 释放（通过[C]氯丙嗪置换测量）对静脉注射吗啡的反应，以及其与吗啡引起的主观效应的关系，在健康、无依赖性阿片类药物经验的参与者中。
最初纳入了 15 名健康男性参与者。每个参与者在不同的日子参加不同的实验。在第 1 次实验中，参与者在诊所接受静脉注射吗啡（10mg/70kg），以确保耐受性。没有不良反应的参与者（n=10）随后在平衡顺序下接受静脉注射吗啡和安慰剂（生理盐水）实验，同时进行[C]氯丙嗪正电子发射断层扫描扫描。评估了主观和生理反应。使用感兴趣区域和体素图像分析来评估[C]氯丙嗪不可置换结合潜能的变化。
吗啡产生了明显的主观和生理效应，并导致[C]氯丙嗪不可置换结合潜能显著降低，特别是在伏隔核和苍白球中，[C]氯丙嗪不可置换结合潜能的变化约为 9%。然而，吗啡的主观效应与 DA 释放没有呈现出简单的相关模式。
这是迄今为止首次在体内提供人类证据，证明腹侧纹状体中的 DA 传递受吗啡影响。需要进一步的研究来充分描绘 DA 对阿片类药物强化作用的贡献。
