BACKGROUND Individuals with cocaine addiction are characterized by under-responsiveness to natural reinforcers. As part of the dopaminergic pathways, the hypothalamus supports motivated behaviors. Rodent studies suggested inter-related roles of the hypothalamus in regulating drug and food intake. However, few studies have investigated hypothalamic responses to drugs and food or related cues in humans. METHODS We examined regional responses in 20 cocaine-dependent and 24 healthy control participants exposed to cocaine/food (cocaine dependent) and food (healthy control) vs neutral cues during functional magnetic resonance imaging. We examined the relationship between imaging findings and clinical variables and performed mediation analyses to examine the inter-relationships between cue-related activations, tonic cocaine craving, and recent cocaine use. RESULTS At a corrected threshold, cocaine-dependent participants demonstrated higher activation to cocaine than to food cues in the hypothalamus, inferior parietal cortex, and visual cortex. Cocaine-dependent participants as compared with healthy control participants also demonstrated higher hypothalamic activation to food cues. Further, the extent of these cue-induced hypothalamic activations was correlated with tonic craving, as assessed by the Cocaine Craving Questionnaire, and days of cocaine use in the prior month. In mediation analyses, hypothalamic activation to cocaine and food cues both completely mediated the relationship between the Cocaine Craving Questionnaire score and days of cocaine use in the past month. CONCLUSIONS The results were consistent with the proposition that the mechanisms of feeding and drug addiction are inter-linked in the hypothalamus and altered in cocaine addiction. The findings provide new evidence in support of hypothalamic dysfunction in cocaine addiction.

中文翻译：

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对可卡因依赖者的可卡因和食物提示下丘脑反应。

背景技术具有可卡因成瘾的个体的特征在于对天然增强剂的反应不足。作为多巴胺能途径的一部分，下丘脑支持动机行为。啮齿动物研究表明，下丘脑在调节药物和食物摄入中的相互关联作用。但是，很少有研究研究下丘脑对人的药物和食物或相关提示的反应。方法我们检查了功能性磁共振成像过程中暴露于可卡因/食物（依赖可卡因）和食物（健康对照）与中性提示的20名可卡因依赖者和24名健康对照参与者的区域反应。我们检查了影像学发现与临床变量之间的关系，并进行了中介分析以检查提示相关激活，对补品可卡因的渴望，和最近使用可卡因。结果在校正的阈值下，可卡因依赖性参与者表现出对可卡因的激活高于对下丘脑，顶叶下皮质和视皮层食物提示的激活。与健康对照参与者相比，可卡因依赖的参与者也表现出更高的下丘脑对食物线索的激活。此外，这些提示诱发的下丘脑激活的程度与可卡因渴望调查表所评估的对补药的渴望以及上个月可卡因的使用天数有关。在调解分析中，下丘脑对可卡因的激活和食物线索都完全介导了可卡因渴望问卷调查得分与过去一个月可卡因使用天数之间的关系。结论该结果与以下假设相吻合：下丘脑中的饮食和成瘾机制相互关联，可卡因成瘾发生改变。这些发现为支持可卡因成瘾的下丘脑功能障碍提供了新的证据。