n-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2-3-dimethoxybenzamide and Tobacco-Use-Disorder

Women differ from men in smoking-related behaviors, among them a greater difficulty in quitting smoking. Unlike female smokers, male smokers have lower striatal dopamine D2-type receptor availability (binding potential, BPND) than nonsmokers and exhibit greater smoking-induced striatal dopamine release. Because dopamine D2-type autoreceptors in the midbrain influence striatal dopamine release, a function that has been linked to addiction, we tested for sex differences in midbrain dopamine D2-type receptor BPND and in relationships between midbrain BPND, nicotine dependence and striatal dopamine D2-type receptor BPND. Positron emission tomography was used with [

Topics: Adolescent; Adult; Analysis of Variance; Benzamides; Female; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Male; Mesencephalon; Middle Aged; Positron-Emission Tomography; Receptors, Dopamine D2; Sex Characteristics; Tobacco Use Disorder; Young Adult

Cigarette smoking induces dopamine release in the striatum, and smoking- or nicotine-induced ventral striatal dopamine release is correlated with nicotine dependence. Smokers also exhibit lower dopamine D2/3 receptor availability in the dorsal striatum than nonsmokers. Negative correlations of striatal dopamine D2/3 receptor availability with smoking exposure and nicotine dependence, therefore, might be expected but have not been tested.. As reported before, lifetime smoking was correlated with nicotine dependence. New findings were that ventral striatal dopamine D2/3 receptor availability was negatively correlated with recent and lifetime smoking and also with nicotine dependence.. The results suggest an effect of smoking on ventral striatal D2/3 dopamine receptors that may contribute to nicotine dependence.

Topics: Adolescent; Adult; Basal Ganglia; Benzamides; Cigarette Smoking; Contrast Media; Cross-Sectional Studies; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Molecular Imaging; Positron-Emission Tomography; Pyrrolidines; Receptors, Dopamine D2; Receptors, Dopamine D3; Smokers; Tobacco Use Disorder; Young Adult

Dopamine (DA) modulates the response of the amygdala. However, the relation between dopaminergic neurotransmission in striatal and extrastriatal brain regions and amygdala reactivity to affective stimuli has not yet been established. To address this issue, we measured DA D2/D3 receptor (DRD2/3) availability in twenty-eight healthy men (nicotine-dependent smokers and never-smokers) using positron emission tomography with [18F]fallypride. In the same group of participants, amygdala response to unpleasant visual stimuli was determined using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. The effects of DRD2/3 availability in emotion-related brain regions and nicotine dependence on amygdala response to unpleasant stimuli were examined by multiple regression analysis. We observed enhanced prefrontal DRD2/3 availability in those individuals with higher amygdala response to unpleasant stimuli. As compared to never-smokers, smokers showed an attenuated amygdala BOLD response to unpleasant stimuli. Thus, individuals with high prefrontal DRD2/3 availability may be more responsive toward aversive and stressful information. Through this mechanism, dopaminergic neurotransmission might influence vulnerability for affective and anxiety disorders. Neuronal reactivity to unpleasant stimuli seems to be reduced by smoking. This observation could explain increased smoking rates in individuals with mental disorders.

Topics: Adult; Amygdala; Benzamides; Brain Mapping; Cerebrovascular Circulation; Emotions; Humans; Magnetic Resonance Imaging; Male; Oxygen; Photic Stimulation; Positron-Emission Tomography; Pyrrolidines; Receptors, Dopamine D2; Receptors, Dopamine D3; Smoking; Tobacco Use Disorder; Visual Perception