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Open Access Research

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

Patrick M Fisher12*, Julie C Price23, Carolyn C Meltzer4, Eydie L Moses-Kolko5, Carl Becker3, Sarah L Berga6 and Ahmad R Hariri78

Author affiliations

1 Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA

2 Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA

3 Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA

4 Department of Radiology, Emory University, Atlanta, Georgia 30322, USA

5 Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA

6 Department of Gynecology & Obstetrics, Emory University, Atlanta, Georgia 30322, USA

7 Department of Neuroscience & Psychology, Duke University, Durham, North Carolina 27710, USA

8 Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina 27710, USA

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Citation and License

Biology of Mood & Anxiety Disorders 2011, 1:2  doi:10.1186/2045-5380-1-2

Published: 27 September 2011

Abstract

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-HT1A and 5-HT2A 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-HT1A and 5-HT2A receptor levels, assessed by positron emission tomography.

Results

5-HT1A binding in the mPFC significantly moderated an inverse correlation between mPFC 5-HT2A binding and threat-related amygdala reactivity. Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low.

Conclusions

Our findings provide evidence that 5-HT1A and 5-HT2A receptors interact to shape serotonergic modulation of a functional circuit between the amygdala and mPFC. The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC.