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

Neuropsychopharmacology. 2009 Jun;34(7):1774-82. doi: 10.1038/npp.2008.235. Epub 2009 Jan 28.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

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