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Heightened D3 Dopamine Receptor Levels in Cocaine Dependence and Contributions to the Addiction Behavioral Phenotype: A Positron Emission Tomography Study with [11C]-(+)-PHNO.
- Source :
- Neuropsychopharmacology; Jan2014, Vol. 39 Issue 2, p321-328, 8p
- Publication Year :
- 2014
-
Abstract
- The dopamine system is a primary treatment target for cocaine dependence (CD), but research on dopaminergic abnormalities (eg, D<subscript>2</subscript> receptor system deficiencies) has so far failed to translate into effective treatment strategies. The D<subscript>3</subscript> receptor system has recently attracted considerable clinical interest, and D<subscript>3</subscript> antagonism is now under investigation as a novel avenue for addiction treatment. The objective here was to evaluate the status and behavioral relevance of the D<subscript>3</subscript> receptor system in CD, using the positron emission tomography (PET) radiotracer [<superscript>11</superscript>C]-(+)-PHNO. Fifteen CD subjects (many actively using, but all abstinent 7-240 days on scan day) and fifteen matched healthy control (HC) subjects completed two PET scans: one with [<superscript>11</superscript>C]-(+)-PHNO to assess D<subscript>3</subscript> receptor binding (BP<subscript>ND</subscript>; calculated regionally using the simplified reference tissue model), and for comparison, a second scan with [<superscript>11</superscript>C]raclopride to assess D<subscript>2/3</subscript> binding. CD subjects also completed a behavioral battery to characterize the addiction behavioral phenotype. CD subjects showed higher [<superscript>11</superscript>C]-(+)-PHNO BP<subscript>ND</subscript> than HC in the substantia nigra, which correlated with behavioral impulsiveness and risky decision making. In contrast, [<superscript>11</superscript>C]raclopride BP<subscript>ND</subscript> was lower across the striatum in CD, consistent with previous literature in 2 week abstinence. The data suggest that in contrast to a D<subscript>2</subscript> deficiency, CD individuals may have heightened D<subscript>3</subscript> receptor levels, which could contribute to addiction-relevant traits. D<subscript>3</subscript> upregulation is emerging as a biomarker in preclinical models of addiction, and human PET studies of this receptor system can help guide novel pharmacological strategies for treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0893133X
- Volume :
- 39
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 92961962
- Full Text :
- https://doi.org/10.1038/npp.2013.192