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

• Type of Material: Article
• Authors: Patrick M. Fisher, University of Pittsburgh; Julie C. Price, University of Pittsburgh; Carolyn Meltzer, Emory University; Eydie L. Moses-Kolko, University of Pittsburgh; Carl Becker, University of Pittsburgh; Sarah L. Berga, Emory University; Ahmad R. Hariri, Duke University
• Language: English
• Date: 2011-09-27
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2011 Fisher et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.biolmoodanxietydisord.com/content/1/1/2
• Title of Journal or Parent Work: Biology of Mood and Anxiety Disorders
• ISSN: 2045-5380
• Volume: 1
• Issue: 2
• Start Page: 1
• End Page: 11
• Grant/Funding Information: We are grateful to our funding sources including the Multi-modal neuroimaging training program fellowship from the National Institute of Drug Addiction (R90 DA023420 to PMF), National Institute of Mental Health (MH067602 and MH064625 to CCM and MH072837 to ARH) and National Alliance for Research on Schizophrenia and Depression (Young Investigator Award to ARH).
• Research Categories: Biology, Genetics; Biology, Neuroscience

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.