August 2013
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59 Citations
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
Positron emission tomography (PET) has convincingly provided in vivo evidence that psychoactive drugs increase dopamine (DA) levels in human brain, a feature thought critical to their reinforcing properties. Some controversy still exists concerning the role of DA in reinforcing smoking behavior and no study has explored whether smoking increases DA concentrations at the D3 receptor, speculated to have a role in nicotine's addictive potential. Here we used PET and [(11)C]-(+)-PHNO ([(11)C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol), to test the hypothesis that smoking increases DA release (decreases [(11)C]-(+)-PHNO binding) in D2-rich striatum and D3-rich extra-striatal regions and is related to craving, withdrawal and smoking behaviour. Ten participants underwent [(11)C]-(+)-PHNO scans after overnight abstinence and after smoking a cigarette. Motivation to smoke (smoking topography), mood and craving were recorded. Smoking significantly decreased self-reported craving, withdrawal, and [(11)C]-(+)-PHNO binding in D2 and D3-rich areas (-12.0% and -15.3%, respectively). We found that motivation to smoke (puff rate) predicted magnitude of DA release in limbic striatum, and the latter was correlated with decreased craving and withdrawal symptoms. This is the first report suggesting that, in humans, DA release is increased in D3 rich areas in response to smoking. Results also support the preferential involvement of the limbic striatum in motivation to smoke, anticipation of pleasure from cigarettes and relief of withdrawal symptoms. We propose that due to the robust effect of smoking on [(11)C]-(+)-PHNO binding, this radiotracer represents an ideal translational tool to investigate novel therapeutic strategies targeting DA transmission.Neuropsychopharmacology accepted article preview online, 19 August 2013. doi:10.1038/npp.2013.209.