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.

Neural arbitration between social and individual learning systems

“…Primate studies found that sustained dopamine neuron activity signaled expected uncertainty ( Fiorillo et al, 2003 ; Schultz, 2010 ; Schultz et al, 2008 ). This was further supported by human pharmacological studies ( Burke et al, 2018 ; Ojala et al, 2018 ) as well as fMRI research showing possible involvement of dopamine in risk taking and of dopaminoceptive regions, such as the caudate, anterior insula, ACC and the medial PFC in uncertainty coding (e.g. Dreher et al, 2006 ; Preuschoff et al, 2008 ; Tobler et al, 2009 ) and social advice predictions under uncertainty ( Henco et al, 2020 ).…”

Shifting uncertainty intolerance: methylphenidate and attention-deficit hyperactivity disorder

“…In ADHD patients, MPH enhanced the hypoactive vmPFC on placebo comparable to the observed levels of healthy controls 2 . Dopaminergic medications increase risk-taking by changing the subjective weighting of the reward probabilities 34 or by increasing the baseline gambling tendency 35 . In this study, it is very likely to have similar effects where MPH via D1 and α 2 -norepinephrine receptors enhanced the vmPFC activity (one of brain's core valuation system 36 ) and altered the subjective value of the choices.…”

A low dosage of the dopamine D2-receptor antagonist sulpiride affects effort allocation for reward regardless of trait extraversion

“…However, it should be noted that we had predicted an increasing rather than a reducing effect of sulpiride on the average number of clicks based on the assumption that the relatively low dose of 200 mg primarily blocks presynaptic autoreceptors, resulting in a reduction of postsynaptic DA activity (Kuroki et al, 1999;Mereu et al, 1983), thus increasing approach motivation. Studies investigating sulpiride's effects on reward processing and its neurophysiological correlates often use higher dosages of up to 800 mg resulting in predominantly inhibiting effects (Diederen et al, 2017;Ojala et al, 2018;Weber et al, 2016;Eisenegger et al, 2014). However, it might be possible that administering a single dose of sulpiride evokes inhibiting effects even when used in smaller dosages.…”

“…While, for example, Kahnt, Weber, Haker, Robbins, & Tobler (2015) failed to find behavioral changes after the intake of 400 mg amisulpiride within an outcome prediction task, Diederen et al (2017) found that participants' ability to predict future rewards was reduced after intake of 600 mg sulpiride. Ojala et al (2018) reported that the intake of 400 mg of sulpiride reduced healthy participants overweighting of low probabilities within a decision-making task, resulting in less risky choices. Weber et al (2016) found that 400 mg of amisulpiride reduced participants' motivation to choose immediate rewards in a delay-discounting task.…”