Serotonin 2A receptors contribute to the regulation of risk-averse decisions

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

    Research output: Contribution to journalArticlepeer-review


    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. © 2013 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)35-44
    Number of pages9
    Publication statusPublished - Dec 2013


    • Decision-making
    • Frontopolar cortex
    • Ketanserin
    • Pharmacological fMRI
    • Reward
    • Serotonin


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