Is there a way to make more rational decisions in risky situations? Researchers investigate

By Liz Meszaros, MDLinx
Published June 18, 2018

Key Takeaways

Blocking dopamine receptors may make for more rational decisions by both healthy and gambling-addicted individuals, according to results from a recent study accepted for publication in eNeuro.

“Dopamine D2/D3 receptor antagonism shifts probability weighting in the direction of more objective, economically rational decision-making,” wrote the researchers, led by Karita E. Ojala, Donders Institute for Brain, Cognition, and Behavior, Radboud University, Nijmegen, The Netherlands.

With this study, the researchers tested their hypothesis that dopamine may foster risk-taking and pathological gambling by modulating subjective probability weighting during decision making. Specifically, they sought to assess the sensitivity of reward and punishment in pathological gamblers and healthy controls treated with the dopamine D2/D3 receptor antagonist sulpiride.

Dopamine has been linked to pathological gambling, or gambling disorder, which is an urge to gamble continuously despite negative consequences or the desire to stop. Research has shown that more dopamine is released in pathological gamblers than in healthy controls during episodes of gambling.

In a recent study, patients with Parkinson’s disease developed symptoms of pathological gambling after being treated with dopaminergic replacement therapy, especially dopamine D2/D3 receptor agonists. Other researchers have found that pathological gambling is characterized by a hyper-dopaminergic state. How dopamine D2/D3 receptor activity encourages or fosters pathological gambling, however, remains unknown.

In this double-blind, counter-balanced design study, Dr. Ojala and colleagues included 21 healthy controls and compared them with 16 pathological gamblers. Subjects were tasked with a decision-making exercise in which they chose between a guaranteed amount of money that was either a set gain or a set loss, and a gamble that was either pure gain or pure loss.

In each series of decisions, the guaranteed amount offered on the first trial corresponded to the expected value of the gamble. In each subsequent trial, this amount was adjusted based on the subjects’ previous choice: it increased if they chose the gamble and decreased if they chose the guaranteed option.

Each subject completed the task twice, first after being given a placebo, and then after taking sulpiride (400 mg).

“Sulpiride was chosen as the dopamine-modulating drug in this study based on a few reasons. First, it is one of the most selective agents acting on dopamine D2/D3 receptors. As mentioned earlier, D2/D3 agents are known to cause pathological gambling symptoms in a subset of patients with Parkinson's disease. Moreover, sulpiride has been shown to modulate the sensitivity to reward and punishment during learning in human studies (Eisenegger et al., 2014; van der Schaaf et al., 2014),” wrote the researchers.

Dr. Ojala and colleagues used a prospect theory modelling approach—which holds that people make decisions based on the potential value of losses and gains and not on final outcome and attempts to model real-life choices instead of optimal decisions. They then estimated subjects’ sensitivity to monetary outcomes and their subjective probability weighting.

They found that subjects had distortions in their subjective weighting of probabilities, with a tendency to overweight low probabilities and to underweight moderate-to-high probabilities. This distortion was attenuated in the gain domain when subjects were given sulpiride.

Their probability weighting was not different when taking placebo compared with sulpiride.

Subjects who were gamblers, however, showed consistent underweighting of losing probabilities when taking placebo. Thus, researchers concluded, the antagonism of dopamine D2/D3 receptors may change the ability to consider and weight probabilities of gain and make for more objective and economically rational decisions.

“We found that selectively blocking dopamine D2/D3 receptors diminished the typically observed distortion of winning probabilities, characterized by an overweighting of low probabilities and underweighting of high probabilities. This made participants more linear in their subjective estimation of probabilities and thus more rational in their decision-making behavior. Healthy participants and pathological gamblers did not differ in their risk-taking behavior, except in the placebo condition in which gamblers consistently underweighted losing probabilities,” concluded the authors.

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