The Effect of Treatment with Guanfacine, an Alpha2 Adrenergic Agonist, on Dopaminergic Tone in Tobacco Smokers: An [ 11 C]FLB457 PET Study.

Autor: Sandiego CM; Department of Psychiatry, Yale University, New Haven, CT, USA.; PET Center, Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA., Matuskey D; Department of Psychiatry, Yale University, New Haven, CT, USA.; PET Center, Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA., Lavery M; Department of Psychiatry, Yale University, New Haven, CT, USA., McGovern E; Department of Psychiatry, Yale University, New Haven, CT, USA., Huang Y; PET Center, Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA., Nabulsi N; PET Center, Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA., Ropchan J; PET Center, Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA., Picciotto MR; Department of Psychiatry, Yale University, New Haven, CT, USA., Morris ED; Department of Psychiatry, Yale University, New Haven, CT, USA.; PET Center, Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.; Department of Biomedical Engineering, Yale University, New Haven, CT, USA., McKee SA; Department of Psychiatry, Yale University, New Haven, CT, USA., Cosgrove KP; Department of Psychiatry, Yale University, New Haven, CT, USA.; PET Center, Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2018 Apr; Vol. 43 (5), pp. 1052-1058. Date of Electronic Publication: 2017 Sep 25.
DOI: 10.1038/npp.2017.223
Abstrakt: Guanfacine, a noradrenergic alpha2a agonist, reduced tobacco smoking in a 4-week trial and in animal models has been shown to reduce cortical dopamine release, which is critically involved in the reinforcing effect of tobacco smoking. We measured amphetamine-induced extrastriatal dopamine release before and after treatment with guanfacine with [ 11 C]FLB457, a dopamine D 2 /D 3 receptor radiotracer, and positron emission tomography (PET). Sixteen tobacco smokers had one set of [ 11 C]FLB457 PET scans on the same day, one before and one at 2.5-3 h after amphetamine (0.4-0.5 mg/kg, PO). A subset (n=12) then underwent guanfacine treatment (3 mg/day for 3 weeks) and the set of scans were repeated. [ 11 C]FLB457-binding potential (BP ND ) was measured pre- and post amphetamine in extrastriatal brain regions. The fractional change in BP ND after vs before amphetamine (Δ BP ND ) is an indirect measure of DA release and was compared between the untreated and guanfacine-treated conditions. Guanfacine treatment attenuated amphetamine-induced DA release; however, the change was due to a global 8% decrease in baseline BP ND from the untreated to the guanfacine-treated condition. Chronic guanfacine treatment reduced [ 11 C]FLB457 BP ND in tobacco smokers, suggesting an increase in dopaminergic tone. Guanfacine-induced normalization of dopamine signaling may be an important mesocortical mechanism contributing to its ability to aid in tobacco smoking cessation.
Databáze: MEDLINE
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