Cue-induced cocaine craving: Neuroanatomical specificity for drug users and drug stimuli

Objective: Cocaine-related cues have been hypothesized to perpetuate drug a buse by inducing a craving response that prompts drug-seeking behavior. How ever, the mechanisms, underlying neuroanatomy, and specificity of this neur oanatomy are not yet fully understood. Method: To address these issues, experienced cocaine users (N=17) and compa rison subjects (N=14) underwent functional magnetic resonance imaging while viewing three separate films that portrayed 1) individuals smoking crack c ocaine, 2) outdoor nature scenes, and 3) explicit sexual content. Candidate craving sites were identified as those that showed significant activation in the cocaine users when viewing the cocaine film. These sites were then r equired to show significantly greater activation when contrasted with compa rison subjects viewing the cocaine film (population specificity) and cocain e users viewing the nature film (content specificity). Results: Brain regions that satisfied these criteria were largely left late ralized and included the frontal lobe (medial and middle frontal gyri, bila teral inferior frontal gyrus), parietal lobe (bilateral inferior parietal l obule), insula, and limbic lobe (anterior and posterior cingulate gyrus). O f the 13 regions identified as putative craving sites,just three(anterior c ingulate, right inferior parietal lobule, and the caudate/lateral dorsal nu cleus) showed significantly greater activation during the cocaine film than during the sex film in the cocaine users, which suggests that cocaine cues activated similar neuroanatomical substrates as naturally evocative stimul i in the cocaine users. Finally, contrary to the effects of the cocaine fil m, cocaine users showed a smaller response than the comparison subjects to the sex film. Conclusions: These data suggest that cocaine craving is not associated with a dedicated and unique neuroanatomical circuitry; instead, unique to the c ocaine user is the ability of learned, drug-related cues to produce brain a ctivation comparable to that seen with nondrug evocative stimuli in healthy comparison subjects.