Cocaine Cue-Induced Dopamine Release in Amygdala and Hippocampus: A High-Resolution PET [18F]Fallypride Study in Cocaine Dependent Participants

Drug-related cues are potent triggers for relapse in people with cocaine dependence. Dopamine (DA) release within a limbic network of striatum, amygdala and hippocampus has been implicated in animal studies, but in humans it has only been possible to measure effects in the striatum. The objective here was to measure drug cue-induced DA release in the amygdala and hippocampus using high-resolution PET with [18 F] fallypride. Twelve cocaine-dependent volunteers (mean age: 39.6 +/- 8.0 years; years of cocaine use: 15.9 +/- 7.4) underwent two [F-18] fallypride high-resolution research tomography-PET scans, one with exposure to neutral cues and one with cocaine cues. [F-18] Fallypride non-displaceable-binding potential (BPND) values were derived for five regions of interest (ROI; amygdala, hippocampus, ventral limbic striatum, associative striatum, and sensorimotor striatum). Subjective responses to the cues were measured with visual analog scales and grouped using principal component analysis. Drug cue exposure significantly decreased BPND values in all five ROI in subjects who had a high-, but not low-, craving response (limbic striatum: p = 0.019, associative striatum: p = 0.008, sensorimotor striatum: p = 0.004, amygdala: p = 0.040, and right hippocampus: p = 0.025). Individual differences in the cue-induced craving response predicted the magnitude of [F-18] fallypride responses within the striatum (ventral limbic: r = 0.581, p = 0.048; associative: r = 0.589, p = 0.044; sensorimotor: r = 0.675, p = 0.016). To our knowledge this study provides the first evidence of drug cue-induced DA release in the amygdala and hippocampus in humans. The preferential induction of DA release among high-craving responders suggests that these aspects of the limbic reward network might contribute to drug-seeking behavior.