Abstract
Research has indicated a major role of dopamine in decision-making processes, but the underlying mechanisms remain largely unknown due to inconsistency in effects of dopaminergic drugs. To clarify the impact of dopamine on impulsive choice, we administered 150 mg L-DOPA to 87 healthy adults in a randomized, placebo-controlled, double-blind, crossover study, evaluating performance in four value-based decision-making tasks. We predicted that baseline impulsivity would moderate L-DOPA effects. In support of our hypothesis, L-DOPA had no main effect on impulsive choice, but reduced risk-seeking for gains in more-impulsive subjects. Because L-DOPA effects may be influenced by body weight, we repeated our analyses on data from half of the sample (n = 44) with lower weight, anticipating a stronger effect. In addition to the effect on risk-seeking for gains, low-weight participants also exhibited baseline-dependent effects of L-DOPA on loss aversion and delay discounting. Our results are consistent with the hypothesis of an inverted U-shaped dopamine function in which both low and high extremes of dopamine signaling are associated with high-impulsive choice. Consideration of differential baseline impulsivity and body weight may resolve previous seemingly paradoxical pharmacological results and might deepen our understanding of dopaminergic mechanisms underlying impulsivity.
Highlights
Value-based decision-making is a complex cognitive process that requires balancing potential rewards against their potential costs, and incorporates the probability of obtaining them and/or the delay until gratification
Repeated measures ANCOVA showed no significant differences between placebo and L-DOPA conditions for delay discounting, risk-seeking for gains and losses, or for loss aversion
When restricting the analyses to the 44 low-weight subjects (≤80.5 kg), the interaction between baseline impulsivity (BIS-15) and drug condition significantly predicted delay discounting behavior as well as loss aversion, and had a significant effect on risk-seeking for gains. This result implies that changes in choice behavior on the Delay Discounting, Probability Discounting for Gains and Mixed Gambles tasks depended on baseline impulsivity: participants with lower BIS-15 scores discounted delays more strongly, and became more risk-seeking for gains and more loss averse after having taken L-DOPA, whereas the opposite was detected for participants with higher BIS-15 scores
Summary
Value-based decision-making is a complex cognitive process that requires balancing potential rewards against their potential costs, and incorporates the probability of obtaining them and/or the delay until gratification. Boosting dopaminergic signaling via d-amphetamine (20 mg) decreased delay discounting[10], and administration of the dopamine D2 receptor antagonist quetiapine (150 mg) promoted risk-seeking (in males but not females) in a gambling task[11]. These findings may partly explain why dopamine-enhancing drugs offer therapeutic benefit for patients with ADHD. Higher BIS-11 scores were associated with higher striatal dopamine transporter availability (consistent with lower dopaminergic tone) in healthy men[28] These findings may reflect the ascending limb of an inverted U-shaped function describing the relationship between dopamine activity (increasing from left to right on x-axis) and BIS-11 impulsivity (decreasing from bottom to top on y-axis), assuming that the descending limb did not emerge since acutely overdosed individuals were not tested. Of note, contrasting data have been reported, limited to BIS subscales in small-sample studies[29,30]
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