Abstract
The goal of this study was to determine D1 receptor availability in human cocaine-dependent (CD) subjects and matched healthy controls (HCs). In addition, the CD subjects performed cocaine self-administration sessions in order to explore the association between D1 receptor availability and cocaine-seeking behavior. Twenty-five CD subjects (40±4 years, 19M/6 F) and 23 matched HCs (38±4 years, 19M/4F) were scanned with PET and the radiotracer [11C]NNC 112. During the cocaine self-administration sessions, CD volunteers were given the choice to self-administer cocaine (0, 6, and 12 mg) or to receive a monetary voucher worth $5. D1 receptor availability was measured in the limbic, associative, and sensori-motor striatum in addition to cortical brain regions. No difference in D1 receptor availability was seen between the two groups. A negative association was seen between D1 receptor BPND in the limbic striatum and the choice for the 6 mg dose of cocaine (r=−0.47, p=0.02, corrected for age). These results do not support the hypothesis that cocaine dependence is associated with a reduction in D1 receptor availability in the striatum. However, within the CD subjects, low D1 receptor availability in the ventral striatum was associated with the choice to self-administer cocaine, suggesting that low D1 receptor availability may be associated with an increased risk of relapse in cocaine dependence.
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Acknowledgements
The authors would like to thank Mabel Torres, Erica Scher, Ingrid Gelbard-Stokes, Elizabeth Hackett, and Hemant Belani for their excellent technical assistance. This study was supported by the Public Health Service NIDA PA50 DA 09236, NIDA K23 DA00483, and NIH M01RR00645.
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The authors report no conflicts of interest associated with the content of this paper.
Diana Martinez: no disclosures.
Mark Slifstein: received compensation for professional services from Glaxo-Smith-Kline, Amgen, and Yale University.
Rajesh Narendran: no disclosures.
Richard W Foltin: no disclosures.
Allegra Broft : no disclosures.
Dah-Ren Hwang: currently an employee of Amgen.
Audrey Perez: no disclosures.
Anissa Abi-Dargham: received compensation for professional services from Bristol Meyers Squibb-Otsuka, Sanofi-Aventis, Vanda Pharmaceuticals, Eli Lilly and Company.
Herbert D Kleber: no disclosures.
Marc Laruelle: currently an employee of Glaxo-Smith-Kline.
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Martinez, D., Slifstein, M., Narendran, R. et al. Dopamine D1 Receptors in Cocaine Dependence Measured with PET and the Choice to Self-Administer Cocaine. Neuropsychopharmacol 34, 1774–1782 (2009). https://doi.org/10.1038/npp.2008.235
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DOI: https://doi.org/10.1038/npp.2008.235
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