Expectancy of physical and social pleasure (PSP) promotes excessive drinking despite the potential aversive effects of misuse, suggesting an imbalance in the response to reward and pain in alcohol seeking. Here, we investigated the competing roles of the reward and pain circuits in PSP expectancy and problem drinking in humans. Using fMRI data during resting (n = 180) and during alcohol cue exposure (n = 71), we examined the antagonistic effects of the reward-related medial orbitofrontal cortex (mOFC) and pain-related periaqueductal gray (PAG) connectivities on PSP expectancy and drinking severity. The two regions’ connectivity maps and strengths were characterized to assess their shared substrates and net relationship with PSP expectancy. We evaluated mediation and path models to further delineate how mOFC and PAG connectivities interacted through the shared substrates to differentially impact expectancy and alcohol use. During resting, whole-brain regressions showed mOFC connectivity in positive and PAG connectivity in negative association with PSP scores, with convergence in the precentral gyrus (PrCG). Notably, greater PAG-PrCG relative to mOFC-PrCG connectivity strength predicted lower PSP expectancy. During the alcohol cue exposure task, the net strength of the PAG vs. mOFC cue-elicited connectivity with the occipital cortex again negatively predicted PSP expectancy. Finally, mediation and path models revealed that the PAG and mOFC connectivities indirectly and antagonistically modulated problem drinking via their opposing influences on expectancy and craving. Thus, the pain and reward circuits exhibit functional antagonism such that the mOFC connectivity increases expectancy of drinking pleasure whereas the PAG serves to counter that effect.

尽管滥用可能会产生厌恶作用，但对身体和社交愉悦（PSP）的期望会促进过度饮酒，这表明在寻求酒精时对奖励和痛苦的反应不平衡。在这里，我们研究了奖励和疼痛回路在人类 PSP 预期和饮酒问题中的竞争作用。使用休息期间 ( n  = 180) 和酒精提示暴露期间 ( n  = 71) 的功能磁共振成像数据，我们检查了奖励相关的内侧眶额皮质 (mOFC) 和疼痛相关的导水管周围灰质 (PAG) 连接对 PSP 预期的拮抗作用和饮酒严重程度。对两个区域的连通图和强度进行了表征，以评估它们的共享基质以及与 PSP 预期的净关系。我们评估了中介和路径模型，以进一步描述 mOFC 和 PAG 连接如何通过共享基质相互作用，从而对预期和酒精使用产生不同的影响。静息期间，全脑回归显示 mOFC 连接与 PSP 评分呈正相关，PAG 连接与 PSP 评分呈负相关，并在中央前回 (PrCG) 中收敛。值得注意的是，PAG-PrCG 相对于 mOFC-PrCG 连接强度越大，预示着 PSP 预期越低。在酒精线索暴露任务中，PAG 与 mOFC 线索引发的与枕叶皮层的连接的净强度再次对 PSP 预期产生负面预测。最后，中介和路径模型表明，PAG 和 mOFC 连接通过对期望和渴望的相反影响，间接和拮抗地调节问题饮酒。因此，疼痛和奖励回路表现出功能拮抗作用，使得 mOFC 连接性增加了饮酒乐趣的预期，而 PAG 则起到抵消这种作用的作用。