File(s) under permanent embargo
In vivo imaging of cerebral dopamine D3 receptors in alcoholism
journal contribution
posted on 2023-06-09, 17:56 authored by David Erritzoe, Andri Tziortzi, David Bargiela, Alessandro ColasantiAlessandro Colasanti, Graham E Searle, Roger N Gunn, John D Beaver, Adam Waldman, David J Nutt, Massimo Bani, Emilio Merlo-pich, Eugenii A Rabiner, Anne Lingford-HughesAnimal studies support the role of the dopamine D3 receptor (DRD3) in alcohol reinforcement or liking. Sustained voluntary alcohol drinking in rats has been associated with an upregulation of striatal DRD3 gene expression and selective blockade of DRD3 reduces ethanol preference, consumption, and cue-induced reinstatement. In vivo measurement of DRD3 in the living human brain has not been possible until recently owing to a lack of suitable tools. In this study, DRD3 status was assessed for the first time in human alcohol addiction. Brain DRD3 availability was compared between 16 male abstinent alcohol-dependent patients and 13 healthy non-dependent age-matched males using the DRD3-preferring agonist positron emission tomography (PET) radioligand [11C]PHNO with and without blockade with a selective DRD3 antagonist (GSK598809 60?mg p.o.). In striatal regions of interest, where the [11C]PHNO PET signal represents primarily DRD2 binding, no differences were seen in [11C]PHNO binding between the groups at baseline. However, baseline [11C]PHNO binding was higher in alcohol-dependent patients in hypothalamus (VT: 16.5±4 vs 13.7±2.9, p=0.040), a region in which the [11C]PHNO signal almost entirely reflects DRD3 availability. The reductions in regional receptor binding (VT) following a single oral dose of GSK598809 (60?mg) were consistent with those observed in previous studies across all regions. There were no differences in regional changes in VT following DRD3 blockade between the two groups, indicating that the regional fractions of DRD3 are similar in the two groups, and the increased [11C]PHNO binding in the hypothalamus in alcohol-dependent patients is explained by elevated DRD3 in this group. Although we found no difference between alcohol-dependent patients and controls in striatal DRD3 levels, increased DRD3 binding in the hypothalamus of alcohol-dependent patients was observed. This may be relevant to the development of future therapeutic strategies to treat alcohol abuse.
History
Publication status
- Published
File Version
- Published version
Journal
NeuropsychopharmacologyISSN
0893-133XPublisher
Springer NatureExternal DOI
Volume
39Page range
1703-1712Department affiliated with
- BSMS Neuroscience Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2019-05-31First Compliant Deposit (FCD) Date
2019-05-31Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC