1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet5 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
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.
Journal of Psychopharmacology (oxford, England), 2013, Vol 27, Issue 10, p. 903-914