J Psychiatry Neurosci 2016;41(5):322-30
Michele S. Milella, MD; Aryandokht Fotros, MD, MSc; Paul Gravel, PhD; Kevin F. Casey, PhD; Kevin Larcher, MEng; Jeroen A.J. Verhaeghe, PhD; Sylvia M.L. Cox, PhD; Andrew J. Reader, PhD; Alain Dagher, MD; Chawki Benkelfat, MD; Marco Leyton, PhD
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.
Submitted June 1, 2015; Revised Sept. 9, 2015; Accepted Oct. 19, 2015; Early-released Feb. 23, 2016
Acknowledgements: This work was supported by an operating grant to M. Leyton from the Canadian Institutes of Health Research (MOP-36429). The authors thank the personnel at the McConnell Brain Imaging Centre for technical assistance.
Affiliations: From the Department of Psychiatry, McGill University, Montreal, Que. Canada (Milella, Cox, Benkelfat, Leyton); the Department of Psychiatry, University of California San Diego, San Diego, Calif., USA (Fotros); the Department of Biomedical Engineering, McGill University, Montreal, Que., Canada (Gravel, Reader); Ste-Justine Hospital Research Center, Université de Montréal, Montreal, Que., Canada (Casey); the Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada (Larcher, Dagher, Benkelfat, Leyton); the Molecular Imaging Center, University of Antwerp, Antwerp, Belgium (Verhaeghe); the Division of Imaging Sciences and Biomedical Engineering, Department of Biomedical Engineering, King’s College London, St. Thomas’ Hospital, London, UK (Reader); and the Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Que., Canada (Leyton).
Competing interests: M. Leyton declares having received operating funds through his institution from GlaxoSmithKline in 2006–2007 to conduct a study on naltrexone. No other competing interests declared.
Contributors: A. Fotros, S. Cox, A Dagher, C. Benkelfat and M. Leyton designed the study. A. Fotros, J. Verhaeghe, S. Cox, A. Reader and M. Leyton acquired the data, which M. Milella, P. Gravel, K. Casey, K. Larcher and M. Leyton analyzed. M. Milella, K. Larcher and M. Leyton wrote the article, which all authors reviewed and approved for publication.
Correspondence to: M. Leyton, Department of Psychiatry, McGill University, 1033 Pine Ave. West, Montreal QC, Canada, H3A 1A1; firstname.lastname@example.org