Journal Article

Regional and source-based patterns of 11C-(+)-PHNO binding potential reveal concurrent alterations in dopamine D2and D3receptor availability in cocaine-use disorder

Gaiser, Edward C, Worhunsky, Patrick D, Matuskey, David, Angarita, Gustavo A, Malison, Robert T, Nabulsi, Nabeel, Potenza, Marc N, Carson, Richard E, Gallezot, Jean-Dominique, Calhoun, Vince D

2017

Overview

Dopamine type 2 and type 3 receptors (D2R/D3R) appear critical to addictive disorders. Cocaine-use disorder (CUD) is associated with lower D2R availability and greater D3R availability in regions primarily expressing D2R or D3R concentrations, respectively. However, these CUD-related alterations in D2R and D3R have not been concurrently detected using available dopaminergic radioligands. Furthermore, receptor availability in regions of mixed D2R/D3R concentration in CUD remains unclear. The current study aimed to extend investigations of CUD-related alterations in D2R and D3R availability using regional and source-based analyses of [11C]-(+)-PHNO positron emission tomography (PET) of 26 individuals with CUD and 26 matched healthy comparison (HC) participants. Regional analysis detected greater binding potential (BPND) in CUD in the midbrain, consistent with prior [11C]-(+)-PHNO research, and lowerBPNDin CUD in the dorsal striatum, consistent with research using non-selective D2R/D3R radiotracers. Exploratory independent component analysis (ICA) identified three sources ofBPND(striatopallidal, pallidonigral, and mesoaccumbens sources) that represent systems of brain regions displaying coherent variation in receptor availability. The striatopallidal source was associated with estimates of regional D2R-related proportions ofBPND(calculated using independent reports of [11C]-(+)-PHNO receptor binding fractions), was lower in intensity in CUD and negatively associated with years of cocaine use. By comparison, the pallidonigral source was associated with estimates of regional D3R distribution, was greater in intensity in CUD and positively associated with years of cocaine use. The current study extends previous D2R/D3R research in CUD, demonstrating both lowerBPNDin the D2R-rich dorsal striatum and greaterBPNDin the D3R-rich midbrain using a single radiotracer. In addition, exploratory ICA identified sources of [11C]-(+)-PHNOBPNDthat were correlated with regional estimates of D2R-related and D3R-related proportions ofBPND, were consistent with regional differences in CUD, and suggest receptor alterations in CUD may also be present in regions of mixed D2R/D3R concentration.

• Publisher: Elsevier Limited
• Subject: Addictions / Cocaine / Dopamine / Drug dosages / Funding / Medical imaging / Studies