Cocaine-related cues elicit craving and activate cortical circuits relevant to episodic memory

Stimuli that regularly accompany drug use are thought to contribute to addiction. Because one of these responses, drug craving, has been identified as contributing to relapse, curbing or eliminating drug craving is a goal in the development of medications for drug abuse. As yet, the biological basis for drug craving has not been elucidated. The present study, therefore, sought to identify the brain circuits that mediate cocaine craving when human subjects are presented with cues associated with cocaine abuse. Measurements of regional cerebral metabolic rates for glucose (rCMRglc) using the [F-18]fluorodeoxyglucose (FDG) method and positron emission tomography were paired with psychophysiological and self-report assessments in cocaine abusers and naive control subjects during two experimental sessions. In the first session, subjects were presented with a neutral stimulus complex, including a videotape on arts and crafts; during the second, a cocaine-related stimulus complex (videotape on cocaine-related activity and paraphernalia; presence of paraphernalia and a small amount of cocaine) was presented. Data from 12 cocaine abusers, but not 5 naive controls, showed increases in self-reports of craving and overall EEG arousal during presentation of the cocaine-related stimuli. These stimuli produced no subcortical rCMRglc effects, but selectively increased rCMRglc (compared with values in the neutral session) in the prefrontal, parietal, posterior cingulate, and occipital cortices of cocaine abusers, but not in naïve controls. The pattern of activation suggested that reactivity to cocaine-related stimuli involved circuits important in episodic memory.