Citation

Macoveanu J, Rowe JB, Hornboll B, Elliott R, Paulson OB, Knudsen GM, Siebner HR. Neuroimage 2013; 83: 35-44.

Affiliation

Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark; Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: julianm@drcmr.dk.

Copyright

(Copyright © 2013, Elsevier Publishing)

DOI

10.1016/j.neuroimage.2013.06.063

PMID

23810974

Abstract

Pharmacological studies point to a role of the neurotransmitter serotonin (5-HT) in regulating the preference for risky decisions, yet the functional contribution of specific 5-HT receptors remains to be clarified. We used pharmacological fMRI to investigate the role of the 5-HT2A receptors in processing negative outcomes and regulating risk-averse behavior. During fMRI, twenty healthy volunteers performed a gambling task under two conditions: with or without blocking the 5-HT2A receptors. The volunteers repeatedly chose between small, likely rewards and large, unlikely rewards. Choices were balanced in terms of expected utility and potential loss. Acute blockade of the 5-HT2A receptors with ketanserin made participants more risk-averse. Ketanserin selectively reduced the neural response of the frontopolar cortex to negative outcomes that were caused by low-risk choices and were associated with large missed rewards. In the context of normal 5-HT2A receptor function, ventral striatum displayed a stronger response to low-risk negative outcomes in risk-taking as opposed to risk-averse individuals. This (negative) correlation between the striatal response to low-risk negative outcomes and risk-averse choice behavior was abolished by 5-HT2A receptor blockade. The results provide the first evidence for a critical role of 5-HT2A receptor function in regulating risk-averse behavior. We suggest that the 5-HT2A receptor system facilitates risk-taking behavior by modulating the outcome evaluation of "missed" reward. These results have implications for understanding the neural basis of abnormal risk-taking behavior, for instance in pathological gamblers.

Language: en