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.

Figure 1

(A) Mean BPND of all 28 subjects. In the regions of interest (ROIs), mean BPND was highest in the basal ganglia/striatum and lowest in the prefrontal cortex. (B) ROIs from which mean BPND were extracted. ROIs include the amygdala (green); emotion‐related parts of the frontal cortex (red); the basal ganglia/striatum including caudate, putamen, and globus pallidus (blue); and the thalamus (yellow). (C) Distributions of BPND in the ROIs. Mean BPND were normally distributed in all ROIs. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

Significant interactions from SPM multiple linear regression analysis: mean prefrontal dopamine receptor availability positively correlates with amygdala BOLD signal change (−27, −6, −18) in response to unpleasant stimuli (panel A). Nonsmokers compared to smokers showed enhanced amygdala BOLD response (24, −9, −15) to unpleasant stimuli (panel B). To illustrate these significant associations, the scatter plot in panel A shows the partial correlation of prefrontal [18F]FP binding potential (BPND) and amygdala BOLD signal change controlling for striatal [18F]FP BPND and smoking status: r = 0.59, P = 0.001. The scatter plot in panel B shows the semipartial correlation of smoking status and amygdala BOLD signal change controlling for prefrontal and striatal [18F]FP BPND: r = 0.49, P = 0.009. Note that unstandardized residuals are displayed. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]