Molla Hanna, DeBrosse Joseph, Keedy Sarah, Lee Royce, de Wit Harriet
Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
Neuropsychopharmacology. 2025 Apr 23. doi: 10.1038/s41386-025-02110-6.
Stimulants enhance dopamine function, affecting diverse aspects of reward function from neural processing of reward cues to feelings of well-being in humans. However, little is known about the relationships among different measures of reward function. Understanding relationships among different indices of reward processing could provide insight into the processes that control motivated behavior. The present study examined the effects of a single dose of methamphetamine on two measures of reward in healthy adults: feelings of well-being and neural activation with reward-related stimuli. In a randomized, within-subject, double-blind study, 88 healthy men and women received a single 20 mg oral dose of methamphetamine (MA) and placebo, across two sessions. Regional activations to reward-related cues were assessed using fMRI during the Monetary Incentive Delay task, and positive subjective effects of MA were assessed using standardized questionnaires. As expected, MA increased euphoria and feelings of well-being. MA had minimal effects on neural activation during either anticipation or receipt of reward, but it significantly increased ventral striatal activation during anticipation of monetary loss, suggesting heightened salience of loss-related cues. As reported previously, caudate activation during reward anticipation during the non-drug (placebo) session was correlated with euphoria induced by MA (on the MA session). However, this correlation between cue-induced neural activation and euphoria was not apparent on the MA session. Thus, MA-induced euphoria was related to reward cue-elicited neural activation only when participants were tested without the drug. MA increased neural reactivity to loss, and this was not correlated with euphoria. These findings suggest that MA can dampen reward-related neural activity normally detected in the drug-free state, and that it enhances brain responses to loss. Further research is needed to determine how neural responses to reward or loss cues are related to feelings of well-being, and how either of these affect reward-related behavior.
兴奋剂会增强多巴胺功能，影响奖励功能的多个方面，从奖励线索的神经处理到人类的幸福感。然而，对于奖励功能的不同测量方法之间的关系，我们知之甚少。了解奖励处理的不同指标之间的关系，有助于深入了解控制动机行为的过程。本研究考察了单剂量甲基苯丙胺对健康成年人两种奖励测量指标的影响：幸福感以及与奖励相关刺激的神经激活。在一项随机、受试者内、双盲研究中，88名健康男性和女性在两个实验环节中分别接受了单次20毫克口服甲基苯丙胺（MA）和安慰剂。在金钱激励延迟任务期间，使用功能磁共振成像（fMRI）评估与奖励相关线索的区域激活情况，并使用标准化问卷评估MA的积极主观效应。正如预期的那样，MA增加了欣快感和幸福感。MA对奖励预期或获得期间的神经激活影响极小，但在预期金钱损失期间，它显著增加了腹侧纹状体的激活，表明与损失相关线索的显著性增强。正如之前报道的那样，在非药物（安慰剂）实验环节中奖励预期期间的尾状核激活与MA诱导的欣快感（在MA实验环节中）相关。然而，在MA实验环节中，线索诱导的神经激活与欣快感之间的这种相关性并不明显。因此，只有在参与者未服用药物的情况下进行测试时，MA诱导的欣快感才与奖励线索引发的神经激活有关。MA增加了对损失的神经反应性，且这与欣快感无关。这些发现表明，MA可能会抑制在无药物状态下通常检测到的与奖励相关的神经活动，并且它会增强大脑对损失的反应。需要进一步研究来确定对奖励或损失线索的神经反应如何与幸福感相关，以及这两者如何影响与奖励相关的行为。
