title: Dopamine, locus of control, and the exploration-exploitation tradeoff.
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.
authors: 1] Department of Neurology, University of California, San Francisco, CA, USA [2] Ernest Gallo Clinic & Research Center, Emeryville, CA, USA [3] Department of Neurology, VA Northern California Health Care System, Martinez, CA, USA.
authors: Andrew S
authors: AS
authors: Kayser
authors: 1] Department of Neurology, University of California, San Francisco, CA, USA [2] Ernest Gallo Clinic & Research Center, Emeryville, CA, USA.
authors: Jennifer M
authors: JM
authors: Mitchell
authors: 1] Department of Neurology, University of California, San Francisco, CA, USA [2] Ernest Gallo Clinic & Research Center, Emeryville, CA, USA.
authors: Dawn
authors: D
authors: Weinstein
authors: Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, RI, USA.
authors: Michael J
authors: MJ
authors: Frank
mesh_terms: D000328:Adult; D001577:Benzophenones / Q000494:pharmacology*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007389:Internal-External Control; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009596:Nitrophenols / Q000494:pharmacology*; D012201:Reward; D000077867:Tolcapone; D035501:Uncertainty; D055815:Young Adult
chemical_list: D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D009596:Nitrophenols; D000077867:Tolcapone; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D004298:Dopamine