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 [ 18 F]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. Hum Brain Mapp 31:716-726,

Sex differences in striatal dopamine D2/D3 receptor availability in smokers and non-smokers

“…The study did not allow differentiation between differences in D2/D3 dopamine-receptor density or in intrasynaptic dopamine concentration as underlying factors for the significant differences we found in D2/D3 dopamine-receptor availability between the groups. Our sample sizes were small which limited our ability to find significant differences in D2/D3 dopamine-receptor availability in extrastriatal regions between the groups as was previously shown (Kobiella et al , 2010). We also did not control for phases of the menstrual cycle in our female participants.…”

The dopaminergic response to acute stress in health and psychopathology: A systematic review

“…Conversely, high baseline DA D2/D3 receptor availability (e.g. low tonic DAergic activity) throughout the PFC is related to increased amygdala BOLD reactivity to unpleasant stimuli (Kobiella et al, 2010). These findings strengthen speculations about the role of the mPFC and, specifically, mPFC DAergic activity in functions such as threat monitoring and evaluation of threat levels.…”

DRD2 polymorphisms modulate reward and emotion processing, dopamine neurotransmission and openness to experience

“…Consistent with an effect of DA on emotional regulation, Parkinson disease patients show impairment of emotional expression recognition (Lawrence et al, 2007). Moreover, prefrontal DA D 2/3 receptor availability, as measured with PET and [ 18 F]fallypride, has been recently associated with greater amygdala responses to unpleasant visual stimuli during fMRI (Kobiella et al, 2010). …”

“…Evidence from animal studies (Berridge and Robinson, 1998; Hamidovic et al, 2009; Ikemoto and Panksepp, 1999) and growing evidence from human in vivo imaging studies (Badgaiyan, 2010; Schott et al, 2008; Kobiella et al, 2010) suggest that dopamine (DA) neurotransmission is critically involved in incentive-motivational mechanisms (Schultz, 2006; Wise, 2004) but also in responses to salient aversive stimuli (Horvitz, 2000; Thierry et al, 1976), in addition to its more traditional roles in cognitive and motor function. Recent literature has linked variation in genes related to DA function ( COMT, DAT and D4 ) with reward (Aarts et al, 2010; Camara et al, 2010; Dreher et al, 2009; Forbes et al, 2009; Hahn et al, 2010; Krugel et al, 2009; Schmack et al, 2008; Yacubian et al, 2007) and emotional processing phenotypes (Aleman et al, 2008; Herrmann et al, 2009; Rasch et al, 2010; Smolka et al, 2005; Swart et al, 2011; Williams et al, 2010).…”