BACKGROUND Naltrexone is a nonselective opioid receptor antagonist used as a treatment for alcohol use disorder. However, only modest clinical effects have been observed, possibly because of limited knowledge about the biological variables affecting the efficacy of naltrexone. We investigated the potential role of the kappa opioid receptor (KOR) in the therapeutic effect of naltrexone. METHODS A total of 48 non-treatment-seeking heavy drinkers (16 women) who met DSM-IV criteria for alcohol dependence participated in two alcohol drinking paradigms (ADPs) separated by a week of open-label naltrexone (100 mg daily). Craving, assessed with the Alcohol Urge Questionnaire and the Yale Craving Scale, and drinking behavior were recorded in each ADP. Prior to naltrexone initiation, KOR availability was determined in the amygdala, hippocampus, pallidum, striatum, cingulate cortex, and prefrontal cortex using positron emission tomography with [11C]LY2795050. RESULTS Participants reported lower levels of craving (Yale Craving Scale: -11 ± 1, p < .0001; Alcohol Urge Questionnaire: -6 ± 0.6, p < .0001) and consumed fewer drinks (-3.7 ± 4, p < .0001) during the second ADP following naltrexone therapy. The observed reduction in drinking was negatively associated with baseline KOR availability in the striatum (p = .005), pallidum (p = .023), and cingulate cortex (p = .018). Voxelwise analysis identified clusters in the bilateral insula, prefrontal, and cingulate cortex associated with the reduction in drinking (p < .0001). In addition, KOR availability in all evaluated brain regions was associated with craving measured in both ADPs. CONCLUSIONS The KOR is implicated in drinking and craving following naltrexone therapy in alcohol use disorder.

中文翻译：

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κ阿片受体与纳曲酮诱导的饮酒和渴望减少有关

背景纳曲酮是一种非选择性阿片受体拮抗剂，用于治疗酒精使用障碍。然而，仅观察到适度的临床效果，可能是因为对影响纳曲酮疗效的生物学变量的了解有限。我们研究了 kappa 阿片受体 (KOR) 在纳曲酮治疗效果中的潜在作用。方法 共有 48 名符合 DSM-IV 酒精依赖标准的非寻求治疗的重度饮酒者（16 名女性）参加了两个酒精饮用范式 (ADP)，间隔一周的开放标签纳曲酮（每天 100 毫克）。每个 ADP 都记录了渴望，通过酒精渴望问卷和耶鲁渴望量表进行评估，以及饮酒行为。在纳曲酮开始之前，在杏仁核、海马、苍白球、使用正电子发射断层扫描和 [11C]LY2795050 检测纹状体、扣带皮层和前额叶皮层。结果 参与者报告的渴望水平较低（耶鲁渴望量表：-11 ± 1，p < .0001；酒精冲动问卷：-6 ± 0.6，p < .0001）并且饮用较少的饮料（-3.7 ± 4，p < .0001 ) 在纳曲酮治疗后的第二次 ADP 期间。观察到的饮酒减少与纹状体 (p = .005)、苍白球 (p = .023) 和扣带皮层 (p = .018) 的基线 KOR 可用性呈负相关。体素分析确定了双侧脑岛、前额叶和扣带回皮质中与饮酒减少相关的簇 (p < .0001)。此外，所有评估大脑区域的 KOR 可用性与两种 ADP 中测量的渴望相关。