Abstract
Whether to continue to exploit a source of reward, or to search for a new one of potentially greater value, is a fundamental and underconstrained decision. Recent computational studies of this exploration-exploitation tradeoff have found that variability in exploration across individuals is influenced by a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene, whose protein product degrades synaptically released dopamine. However, these and other genotype–phenotype associations have rarely been causally tested. To directly test this association and to evaluate additional behavioral characteristics, including perceived locus of control (LOC), here we used the COMT inhibitor tolcapone in a randomized, double-blind, counterbalanced, within-subject study of 66 subjects genotyped for the Val158Met allele to assess the hypothesis that reducing COMT enzymatic activity interacts with genotype to increase uncertainty-driven exploration. In keeping with our initial hypothesis, tolcapone led to an increase in exploratory, but not exploitative, behavior in Met/Met rather than Val/Val subjects. Independent of genotype, those subjects with a more external LOC also showed increases in uncertainty-driven exploration on tolcapone relative to placebo. However, we did not replicate our previous finding that Met/Met subjects show greater exploration at baseline. Together these findings support a model in which exploration is hypothesized to have a dopaminergic basis. Moreover, in keeping with findings in other behavioral and cognitive domains, the response to an increase in presumptively frontal dopamine is dependent upon baseline dopamine tone.
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Acknowledgements
We thank Candice Teague for essential help with subject screening, and the subjects themselves for their participation. This research was supported by funding from the Wheeler Center for the Neurobiology of Addiction, the Telemedicine and Advanced Technology Research Center (grants W81XWH-10-1-0231 and W81XWH-11-1-0596 to A.S.K. and J.M.M.) and funds from the state of California (A.S.K. and J.M.M.).
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Kayser, A., Mitchell, J., Weinstein, D. et al. Dopamine, Locus of Control, and the Exploration-Exploitation Tradeoff. Neuropsychopharmacol 40, 454–462 (2015). https://doi.org/10.1038/npp.2014.193
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DOI: https://doi.org/10.1038/npp.2014.193
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