Dopamine D1 receptors in cocaine dependence measured with PET and the choice to self-administer cocaine.

Abstract

The goal of this study was to determine D(1) 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 D(1) 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 [(11)C]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. D(1) receptor availability was measured in the limbic, associative, and sensori-motor striatum in addition to cortical brain regions. No difference in D(1) receptor availability was seen between the two groups. A negative association was seen between D(1) receptor BP(ND) 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 D(1) receptor availability in the striatum. However, within the CD subjects, low D(1) receptor availability in the ventral striatum was associated with the choice to self-administer cocaine, suggesting that low D(1) receptor availability may be associated with an increased risk of relapse in cocaine dependence.

• Authors: Diana Martinez, Mark Slifstein, Rajesh Narendran, Richard W Foltin, Allegra Broft, Dah-Ren Hwang, Audrey Perez, Anissa Abi-Dargham, Marian W Fischman, Herbert D Kleber, Marc Laruelle
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 34 Issue 7 Pg. 1774-82 (Jun 2009) ISSN: 1740-634X [Electronic] England
• PMID: 19177067 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Benzazepines
• Benzofurans
• Dopamine Uptake Inhibitors
• Receptors, Dopamine D1
• NNC 112
• Cocaine

Topics

• Adult
• Benzazepines (metabolism)
• Benzofurans (metabolism)
• Brain Mapping
• Choice Behavior (physiology)
• Cocaine (administration & dosage)
• Cocaine-Related Disorders (diagnostic imaging, pathology, physiopathology)
• Dopamine Uptake Inhibitors (administration & dosage)
• Female
• Humans
• Male
• Middle Aged
• Positron-Emission Tomography
• Receptors, Dopamine D1 (metabolism)
• Reinforcement Schedule
• Self Administration (methods)