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Social Cognitive and Affective Neuroscience Advance Access published online on June 23, 2009
Social Cognitive and Affective Neuroscience, doi:10.1093/scan/nsp020
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© The Author (2009). Published by Oxford University Press. For Permissions, please email: journals.permissions@oxfordjournals.org

Serotonin shapes risky decision making in monkeys

Arwen B. Long1,2, Cynthia M. Kuhn3 and Michael L. Platt1,4

1Department of Neurobiology,2Duke University Medical School,3Department of Pharmacology and Cancer Biology, and 4Centre for Neuroeconomic Studies, Duke University, Durham, NC 27710, USA

Some people love taking risks, while others avoid gambles at all costs. The neural mechanisms underlying individual variation in preference for risky or certain outcomes, however, remain poorly understood. Although behavioral pathologies associated with compulsive gambling, addiction and other psychiatric disorders implicate deficient serotonin signaling in pathological decision making, there is little experimental evidence demonstrating a link between serotonin and risky decision making, in part due to the lack of a good animal model. We used dietary rapid tryptophan depletion (RTD) to acutely lower brain serotonin in three macaques performing a simple gambling task for fluid rewards. To confirm the efficacy of RTD experiments, we measured total plasma tryptophan using high-performance liquid chromatography (HPLC) with electrochemical detection. Reducing brain serotonin synthesis decreased preference for the safe option in a gambling task. Moreover, lowering brain serotonin function significantly decreased the premium required for monkeys to switch their preference to the risky option, suggesting that diminished serotonin signaling enhances the relative subjective value of the risky option. These results implicate serotonin in risk-sensitive decision making and, further, suggest pharmacological therapies for treating pathological risk preferences in disorders such as problem gambling and addiction.

Keywords: serotonin; behavior; risky decision making; macaque; pathological gambling; rapid tryptophan depletion

Correspondence should be addressed to Arwen B. Long, Department of Neurobiology, Duke University, Box 3209, Durham, NC 27710, USA. E-mail: arwen{at}neuro.duke.edu

The authors thank Sheila Roberts and Kara Moore for invaluable assistance, Maria Bartolome for analysis of plasma tryptophan, Tim Hanson for a Matlab algorithm used for macaque behavior analysis and David Fitzpatrick, Scott Huettel, Jill Stowe, Bill Wetsel, Allison McCoy, Jamie Roitman, Robert Deaner, Ben Hayden, O’Dhaniel Mullette-Gilman, Karli Watson, John Pearson, Mike Bendiksby, Sarah Heilbronner, Jeff Klein and Stephen Shepherd for stimulating discussion. The authors also thank two anonymous reviewers for helpful comments. National Institutes of Health grants, including F30MH79555-01 (to A.L.).

Received November 1, 2008. Accepted May 22, 2009.


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