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

Abstract

Background-The serotonin 2A (5-HT 2A ) 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 MRI (fMRI) after 5-HT 2A receptor blockade, while judging the gender of neutral, fearful and angry faces.

(S)-citalopram influences amygdala modulation in healthy subjects: a randomized placebo-controlled double-blind fMRI study using dynamic causal modeling

“…Verification of a lack of differences in (S)-citalopram levels after 10 day administration might suggest that amygdala-OFC connectivity differences between Escitalopram and Citalopram are dependent on the presence of (R)-citalopram. Considering that the serotonergic system is suggested to influence amygdala and OFC connectivity (Hornboll et al, 2013), our results may depend on differing mediation of serotonergic transmission by (R)-citalopram and (S)-citalopram. These findings may therefore offer another possible dimension to existing explanations for clinical efficacy differences between Citalopram and Escitalopram (Cipriani et al, 2009;Yevtushenko et al, 2007).…”

“…In fact, in addition to influencing the behavioral and mood correlates of emotion processing in both healthy controls as well as depressed patients (Merens et al, 2007), modifications of the serotonergic system have been related to functional connectivity changes of emotion processing networks. Blockage of 5HT-2A receptors has been directly linked to an increase in amygdala-OFC connectivity during processing of fearful faces (Hornboll et al, 2013), while application of SSRIs may also result in modulation of connectivity within this network. On a receptor level, Fig.…”

“…For example, ablation of serotonergic transmission by tryptophan depletion results in alteration of amygdala and OFC neural response during emotion and fear processing (Fusar-Poli et al, 2007;Hindi Attar et al, 2012). On a receptor-specific, pharmacologic level, administration of a 5-HT2A antagonist has been shown to reduce OFC activity, but increase the region's functional coupling to the amygdala during processing of fearful faces (Hornboll et al, 2013). However, differences have been shown among SSRIs in the clinical effectiveness they achieve.…”

Behavioral and neural correlates of visual emotion discrimination and empathy in mild cognitive impairment

“…This is further supported by the early presence in dementia of structural and neurochemical changes in amygdala connectivity with the anterior cingulate and orbitofrontal cortices [125][126][127][128][129][130]. In addition, the significant reduction in cortical serotonin 2A receptors in MCI [131,132], normally dense in the orbitofrontal cortex, may be involved in the altered sensitivity to fearful facial expressions, through the feedback regulation from the orbitofrontal cortex to the amygdala [133]. Finally, the fact that mPFC is particularly associated with fearful facial expressions is not surprising.…”

The Center for Integrated Molecular Brain Imaging (Cimbi) database

“…Functional MRI (fMRI) in conjunction with various pharmacological challenges of the 5-HT system has been obtained with emotional faces task (Grady et al, 2013;Hornboll et al, 2013) or a gambling task (Macoveanu et al, 2013b, Macoveanu et al, 2013cMacoveanu et al, 2013a). fMRI has also been investigated in relation to genotype (Fisher et al, 2012) and bright light intervention .…”