Dopamine and Risky Decision-Making in Gambling Disorder

Gambling disorder is a behavioral addiction associated with impairments in value-based decision-making and cognitive control. These functions are thought to be regulated by dopamine within fronto-striatal circuits, but the role of altered dopamine neurotransmission in the etiology of gambling disorder remains controversial. Preliminary evidence suggests that increasing frontal dopamine tone might improve cognitive functioning in gambling disorder. We therefore examined whether increasing frontal dopamine tone via a single dose of the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in human gamblers (n = 14) in a randomized double-blind placebo-controlled crossover study. Data were analyzed using hierarchical Bayesian parameter estimation and a combined risky choice drift diffusion model (DDM). Model comparison revealed a nonlinear mapping from value differences to trial-wise drift rates, confirming recent findings. An increase in risk-taking under tolcapone versus placebo was about five times more likely, given the data, than a decrease [Bayes factor (BF) = 0.2]. Examination of drug effects on diffusion model parameters revealed that an increase in the value dependency of the drift rate under tolcapone was about thirteen times more likely than a decrease (BF = 0.073). In contrast, a reduction in the maximum drift rate under tolcapone was about seven times more likely than an increase (BF = 7.51). Results add to previous work on COMT inhibitors in behavioral addictions and to mounting evidence for the applicability of diffusion models in value-based decision-making. Future work should focus on individual genetic, clinical and cognitive factors that might account for heterogeneity in the effects of COMT inhibition.