Acute serotonin 2A receptor blocking alters the processing of fearful faces in the orbitofrontal cortex and amygdala

Bettina Hornboll, Julian Macoveanu, James Rowe, Rebecca Elliott, Olaf B Paulson, Hartwig R Siebner, Gitte M Knudsen

22 Citationer (Scopus)

Abstract

Background: The serotonin 2A (5-HT2A) receptor has been implicated in neural-processing of emotionally salient information. To elucidate its role in processing of fear and anger, healthy individuals were studied with functional magnetic resonance imaging (fMRI) after 5-HT2A receptor blockade, while judging the gender of neutral, fearful and angry faces. Methods: 5-HT2A receptors were blocked with ketanserin to a variable degree across subjects by adjusting the time between ketanserin-infusion and onset of the fMRI protocol. Neocortical 5-HT2A receptor binding in terms of the binding potential (BPp ) was assessed prior to fMRI with (18)F-altanserin positron emission tomography (PET) and subsequently integrated in the fMRI data analysis. Also functional connectivity analysis was employed to evaluate the effect of ketanserin blocking on connectivity. Results: Compared to a control session, 5-HT2A receptor blockade reduced the neural response to fearful faces in the medial orbitofrontal cortex (OFC), independently of 5-HT2A receptor occupancy or neocortical 5-HT2A receptor BPp . The medial OFC also showed increased functional coupling with the left amygdala during processing of fearful faces depending on the amount of blocked 5-HT2A receptors. Conclusions: 5-HT2A receptor mediated signaling increases the sensitivity of the OFC to fearful facial expressions and regulates the strength of a negative feedback signal from the OFC to amygdala during processing of fearful faces.
OriginalsprogEngelsk
TidsskriftJournal of psychopharmacology
Vol/bind27
Udgave nummer10
Sider (fra-til)903-14
Antal sider12
ISSN0269-8811
DOI
StatusUdgivet - okt. 2013

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