μ Opioid Antagonist Naltrexone Partially Abolishes the Antidepressant Placebo Effect and Reduces Orbitofrontal Cortex Encoding of Reinforcement.
μ Opioid Antagonist Naltrexone Partially Abolishes the Antidepressant Placebo Effect and Reduces Orbitofrontal Cortex Encoding of Reinforcement.
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DOI：
10.1016/j.bpsc.2021.02.009
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Dombrovski AY
中科院分区：
文献类型：
--
作者：
Peciña M;Chen J;Lyew T;Karp JF;Dombrovski AY
与安慰剂止痛一样，抗抑郁剂的安慰剂效应似乎涉及皮质和皮质下内源性阿片信号，但阿片释放影响情绪的机制尚不清楚。眼眶前额叶皮质整合了刺激的各种属性以预测相关结果，与安慰剂效应有关，并富含μ阿片受体。我们假设纳曲酮阻断μ阿片受体将减弱依赖于OFC的抗抑郁剂的安慰剂效应。20名不服用精神药物的严重抑郁障碍(MDD)患者完成了一项随机、双盲、安慰剂对照的交叉研究，其中一次口服50毫克纳曲酮或匹配的安慰剂，就在完成抗抑郁药安慰剂功能磁共振任务的两个疗程之前。这项任务操纵与安慰剂相关的期望及其强化，同时评估预期和实际的情绪改善。在行为上，操纵抗抑郁剂安慰剂的期望及其强化对参与者的期望和情绪评级具有积极的交互作用。高期望值状态下，前额叶皮质背外侧和腹外侧区(dl/vlpfc)以及背侧注意流区被激活。有趣的是，dl/vlpfc大脑反应的增加似乎减弱了抗抑郁剂的安慰剂效应。与安慰剂相比，口服一次剂量的纳曲酮部分消除了期望和强化操作对情绪的交互作用，并阻断了右侧中央OFC(CofC)的强化诱导反应。我们的结果显示，初步证据表明，μ-阿片类COFC通过积极偏向基于强化的安慰剂的价值和增强随后的享乐体验，在抗抑郁安慰剂效应中发挥作用。临床试验编号：NCT04322526
Like placebo analgesia, the antidepressant placebo effect appears to involve cortical and subcortical endogenous opioid signaling, yet the mechanism through which opioid release impacts mood remains unclear. The orbitofrontal cortex (OFC) – which integrates various attributes of a stimulus to predict associated outcomes – has been implicated in placebo effects and is rich in μ-opioid receptors. We hypothesized that naltrexone blockade of μ-opioid receptors would blunt OFC-dependent antidepressant placebo effects. Twenty psychotropic-free patients with Major Depressive Disorder (MDD) completed a randomized, double-blind, placebo-controlled, crossover study of one oral dose of 50mg of naltrexone or matching placebo immediately before completing two sessions of the Antidepressant Placebo fMRI Task. This task manipulates placebo-associated expectancies and their reinforcement while assessing expected and actual mood improvement. Behaviorally, manipulations of antidepressant placebo expectancies and their reinforcement had positive, interactive effects on participants’ expectancy and mood ratings. The high expectancy condition recruited the dorsolateral and ventrolateral prefrontal cortex (dl/vlPFC), as well as dorsal attention stream regions. Interestingly, increased dl/vlPFC brain responses appeared to attenuate the antidepressant placebo effect. The administration of one oral dose of naltrexone, compared to placebo, partially abolished the interaction of the expectancy and reinforcement manipulation on mood and blocked reinforcement-induced responses in the right central OFC (cOFC). Our results show preliminary evidence for the role of μ-opioid cOFC modulation in antidepressant placebo effects by positively biasing the value of placebo based on reinforcement and enhancing subsequent hedonic experiences. Clinical trial number: NCT04322526
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影响因子：
3.5
作者：
Gorgolewski K;Burns CD;Madison C;Clark D;Halchenko YO;Waskom ML;Ghosh SS
通讯作者：
Ghosh SS
影响因子：
3.6
作者：
Delamater, AR;Sclafani, A;Bodnar, RJ
通讯作者：
Bodnar, RJ
DOI：
10.1073/pnas.1104047108
发表时间：
2011-06-21
影响因子：
11.1
作者：
Anderson, Brian A.;Laurent, Patryk A.;Yantis, Steven
通讯作者：
Yantis, Steven
影响因子：
7.4
作者：
Bingel, U;Lorenz, J;Büchel, C
通讯作者：
Büchel, C
影响因子：
16.2
作者：
Eippert, Falk;Bingel, Ulrike;Buechel, Christian
通讯作者：
Buechel, Christian