RT Journal Article SR Electronic T1 Cocaine cue–induced dopamine release in the human prefrontal cortex JF Journal of Psychiatry and Neuroscience JO J Psychiatry Neurosci FD Canadian Medical Association SP 322 OP 330 DO 10.1503/jpn.150207 VO 41 IS 5 A1 Michele S. Milella A1 Aryandokht Fotros A1 Paul Gravel A1 Kevin F. Casey A1 Kevin Larcher A1 Jeroen A.J. Verhaeghe A1 Sylvia M.L. Cox A1 Andrew J. Reader A1 Alain Dagher A1 Chawki Benkelfat A1 Marco Leyton YR 2016 UL http://jpn.ca/content/41/5/322.abstract AB Background: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown.Methods: We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence.Results: Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [18F]fallypride binding potential (BPND) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with BPND changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain BPND values were significantly correlated with changes in BPND within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in BPND and self-reported craving.Limitations: Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release.Conclusion: In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms.