Medial prefrontal cortex serotonin 1A and 2A receptor binding interacts to predict threat-related amygdala reactivity

Background The amygdala and medial prefrontal cortex (mPFC) comprise a key corticolimbic circuit that helps shape individual differences in sensitivity to threat and the related risk for psychopathology. Although serotonin (5-HT) is known to be a key modulator of this circuit, the specific receptors...
Ausführliche Beschreibung

Background The amygdala and medial prefrontal cortex (mPFC) comprise a key corticolimbic circuit that helps shape individual differences in sensitivity to threat and the related risk for psychopathology. Although serotonin (5-HT) is known to be a key modulator of this circuit, the specific receptors mediating this modulation are unclear. The colocalization of 5-$ HT_{1A} $ and 5-$ HT_{2A} $ receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity. Using a multimodal neuroimaging strategy in 39 healthy volunteers, we determined whether threat-related amygdala reactivity, assessed with blood oxygen level-dependent functional magnetic resonance imaging, was significantly predicted by the interaction between mPFC 5-$ HT_{1A} $ and 5-$ HT_{2A} $ receptor levels, assessed by positron emission tomography. Results 5-$ HT_{1A} $ binding in the mPFC significantly moderated an inverse correlation between mPFC 5-$ HT_{2A} $ binding and threat-related amygdala reactivity. Specifically, mPFC 5-$ HT_{2A} $ binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-$ HT_{1A} $ binding was relatively low. Conclusions Our findings provide evidence that 5-$ HT_{1A} $ and 5-$ HT_{2A} $ receptors interact to shape serotonergic modulation of a functional circuit between the amygdala and mPFC. The effect of the interaction between mPFC 5-$ HT_{1A} $ and 5-$ HT_{2A} $ binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC. Ausführliche Beschreibung