title: Human dopamine receptor D2/D3 availability predicts amygdala reactivity to unpleasant stimuli.
abstract: 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.
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kobiella
authors.forename: Sabine
authors.initials: S
authors.lastname: Vollstädt-Klein
authors.forename: Mira
authors.initials: M
authors.lastname: Bühler
authors.forename: Caroline
authors.initials: C
authors.lastname: Graf
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.forename: Nina
authors.initials: N
authors.lastname: Bernow
authors.forename: Igor Y
authors.initials: IY
authors.lastname: Yakushev
authors.forename: Christian
authors.initials: C
authors.lastname: Landvogt
authors.forename: Mathias
authors.initials: M
authors.lastname: Schreckenberger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.forename: Christoph
authors.initials: C
authors.lastname: Fehr
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
mesh_terms: D000328:Adult; D000679:Amygdala / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001549:Benzamides; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D004644:Emotions / Q000502:physiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D049268:Positron-Emission Tomography; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012907:Smoking / Q000503:physiopathology; D014029:Tobacco Use Disorder / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014796:Visual Perception / Q000502:physiology*
chemical_list: D001549:Benzamides; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D010100:Oxygen