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

作者：Hornboll Bettina^*; Macoveanu Julian; Rowe James; Elliott Rebecca; Paulson Olaf B; Siebner Hartwig R; Knudsen Gitte M

来源：Journal of Psychopharmacology, 2013, 27(10): 903-914.

DOI：10.1177/0269881113494106

<jats:sec><jats:title>Background:</jats:title><jats:p> The serotonin 2A (5-HT<jats:sub>2A</jats:sub>) 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-HT<jats:sub>2A</jats:sub> receptor blockade, while judging the gender of neutral, fearful and angry faces. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> 5-HT<jats:sub>2A</jats:sub> 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-HT<jats:sub>2A</jats:sub> receptor binding in terms of the binding potential ( BP<jats:sub>p</jats:sub>) was assessed prior to fMRI with <jats:sup>18</jats:sup>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. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Compared to a control session, 5-HT<jats:sub>2A</jats:sub> receptor blockade reduced the neural response to fearful faces in the medial orbitofrontal cortex (OFC), independently of 5-HT<jats:sub>2A</jats:sub> receptor occupancy or neocortical 5-HT<jats:sub>2A</jats:sub> receptor BP<jats:sub>p</jats:sub>. The medial OFC also showed increased functional coupling with the left amygdala during processing of fearful faces depending on the amount of blocked 5-HT<jats:sub>2A</jats:sub> receptors. </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> 5-HT<jats:sub>2A</jats:sub> 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. </jats:p></jats:sec>

• 出版日期2013-10