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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.

Hypothalamic Responses to Cocaine and Food Cues in Individuals with Cocaine Dependence