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Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making.

ABSTRACT: Dopamine has been associated with risky decision-making, as well as with pathological gambling, a behavioral addiction characterized by excessive risk-taking behavior. However, the specific mechanisms through which dopamine might act to foster risk-taking and pathological gambling remain elusive. Here we test the hypothesis that this might be achieved, in part, via modulation of subjective probability weighting during decision making. Human healthy controls (n = 21) and pathological gamblers (n = 16) played a decision-making task involving choices between sure monetary options and risky gambles both in the gain and loss domains. Each participant played the task twice, either under placebo or the dopamine D2/D3 receptor antagonist sulpiride, in a double-blind counterbalanced design. A prospect theory modelling approach was used to estimate subjective probability weighting and sensitivity to monetary outcomes. Consistent with prospect theory, we found that participants presented a distortion in the subjective weighting of probabilities, i.e., they overweighted low probabilities and underweighted moderate to high probabilities, both in the gain and loss domains. Compared with placebo, sulpiride attenuated this distortion in the gain domain. Across drugs, the groups did not differ in their probability weighting, although gamblers consistently underweighted losing probabilities in the placebo condition. Overall, our results reveal that dopamine D2/D3 receptor antagonism modulates the subjective weighting of probabilities in the gain domain, in the direction of more objective, economically rational decision making.

SUBMITTER: Ojala KE

PROVIDER: S-EPMC5889481 | biostudies-literature | 2018 Mar-Apr

REPOSITORIES: biostudies-literature

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Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making.

Ojala Karita E KE Janssen Lieneke K LK Hashemi Mahur M MM Timmer Monique H M MHM Geurts Dirk E M DEM Ter Huurne Niels P NP Cools Roshan R Sescousse Guillaume G

eNeuro 20180301 2

Dopamine has been associated with risky decision-making, as well as with pathological gambling, a behavioral addiction characterized by excessive risk-taking behavior. However, the specific mechanisms through which dopamine might act to foster risk-taking and pathological gambling remain elusive. Here we test the hypothesis that this might be achieved, in part, via modulation of subjective probability weighting during decision making. Human healthy controls (<i>n</i> = 21) and pathological gambl ...[more]

PMID: 29632870

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Project description:Risky decision-making is the decision made by individuals when they know the probability of each outcome. In order to survive in unpredictable environments, it is necessary for individuals to assess the probability of events occurring to an make appropriate decisions. There are few studies on the neural basis of risky decision-making behavior guided by external cues, which is related to the relative paucity of animal behavioral paradigms. Previous studies have shown that the prefrontal cortex (PFC) plays a key role in risk-based decision-making. The PFC receives projections from the dopamine (DA) system from the ventral tegmental area of the midbrain. The mesocorticolimbic DA system regulates the judgments of reward and value in decision-making. However, the specific receptor mechanism for prefrontal DA regulation of cue-guided risky decision-making behavior remains unclear. Here we established a cue-guided risky decision-making behavioral paradigm (RDM task) to detect the behavior of rats making decisions between a small certain reward and a large uncertain reward in a self-paced manner. The D1 receptor antagonist SCH-23390 (5 mM) or agonist SKF-82958 (5 mM), and the D2 receptor antagonist thioridazine hydrochloride (5 mM) or agonist MLS-1547 (5 mM) was injected into the mPFC, respectively, to investigate how the behavior in the RDM task was changed. The results showed that: (1) rats were able to master the operation of the cue-guided RDM task in a self-paced way; (2) a majority of rats were inclined to choose risk rather than a safe option when the reward expectations were equal; and (3) risk selection was reduced upon inhibition of D1 receptors or stimulation of D2 receptors, but increased upon stimulation of D1 receptors or inhibition of D2 receptors, suggesting that the RDM performance is regulated by D1 and D2 receptors in the mPFC. The present results suggest that DA receptors in the mPFC of rats are involved in regulating cue-guided RDM behavior, with differential involvement of D1 and D2 receptors in the regulation.

Project description:ObjectiveAmong young children excessive externalizing behaviors often predict adolescent conduct and substance use disorders. Adolescents with those disorders show aberrant brain function when choosing between risky or cautious options. We therefore asked whether similarly aberrant brain function during risky decision-making accompanies excessive externalizing behaviors among children, hypothesizing an association between externalizing severity and regional intensity of brain activation during risky decision-making.MethodFifty-eight (58) 9-11 year-old children (both sexes), half community-recruited, half with substance-treated relatives, had parent-rated Child Behavior Checklist Externalizing scores. During fMRI, children repeatedly chose between doing a cautious behavior earning 1 point or a risky behavior that won 5 or lost 10 points. Conservative permutation-based whole-brain regression analyses sought brain regions where, during decision-making, activation significantly associated with externalizing score, with sex, and with their interaction.ResultsBefore risky responses higher externalizing scores were significantly, negatively associated with neural activation (t's: 2.91-4.76) in regions including medial prefrontal cortex (monitors environmental reward-punishment schedules), insula (monitors internal motivating states, e.g., hunger, anxiety), dopaminergic striatal and midbrain structures (anticipate and mediate reward), and cerebellum (where injuries actually induce externalizing behaviors). Before cautious responses there were no significant externalizing:activation associations (except in post hoc exploratory analyses), no significant sex differences in activation, and no significant sex-by-externalizing interactions.ConclusionsAmong children displaying more externalizing behaviors extensive decision-critical brain regions were hypoactive before risky behaviors. Such neural hypoactivity may contribute to the excessive real-life risky decisions that often produce externalizing behaviors. Substance exposure, minimal here, was a very unlikely cause.

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Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making.

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Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making.

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