1. ¹The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
2. ²Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3. ³Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, USA
4. ⁴Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
5. ⁵Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA
6. ⁶Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
7. ⁷Center for Chemical Dependency, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA
8. ⁸PET Center and Center of Functionally Integrative Neuroscience, Aarhus City Hospital, Aarhus University Hospitals, Aarhus University, Aarhus, Denmark
9. ⁹Department of Psychiatry and Behavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
10. ¹⁰Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
11. ¹¹The Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Correspondence: Dr DF Wong, Radiology-Nuclear Medicine, Johns Hopkins University School of Medicine, 601 North Caroline St, JHOC Room 3245, Johns Hopkins Medical Institutions, Baltimore, MD 21287-0807, USA, Tel: +1 410 955 8433, Fax: +1 410 955 0696, E-mail: dfwong@jhmi.edu

¹²Current address: Controlled Substance Staff, Food and Drug Administration, Rockville, MD, USA. Views expressed do not necessarily represent those of FDA; KRB participated as a NIDA postdoctoral fellow.

¹³Current address: Section for Developmental and Affective Neuroscience, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.

¹⁴Current address: Discovery Medicine, AstraZeneca LP, Wilmington, DE, USA.

Received 19 June 2006; Accepted 18 July 2006; Published online 13 September 2006.

Abstract

In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [¹¹C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.