Amping up effort: effects of d-amphetamine on human effort-based decision-making

Abstract

Animal studies suggest the neurotransmitter dopamine (DA) plays an important role in decision-making. In rats, DA depletion decreases tolerance for effort and probability costs, while drugs enhancing DA increase tolerance for these costs. However, data regarding the effect of DA manipulations on effort and probability costs in humans remain scarce. The current study examined acute effects of d-amphetamine, an indirect DA agonist, on willingness of healthy human volunteers to exert effort for monetary rewards at varying levels of reward value and reward probability. Based on preclinical research, we predicted amphetamine would increase exertion of effort, particularly when reward probability was low. Over three sessions, 17 healthy normal adults received placebo, d-amphetamine 10 mg, and 20 mg under counterbalanced double-blind conditions and completed the Effort Expenditure for Rewards Task. Consistent with predictions, amphetamine enhanced willingness to exert effort, particularly when reward probability was lower. Amphetamine did not alter effects of reward magnitude on willingness to exert effort. Amphetamine sped task performance, but its psychomotor effects were not strongly related to its effects on decision-making. This is the first demonstration in humans that dopaminergic manipulations alter willingness to exert effort for rewards. These findings help elucidate neurochemical substrates of choice, with implications for neuropsychiatric diseases characterized by dopaminergic dysfunction and motivational deficits.

Figures

Figure 1.

Schematic diagram of a single EEfRT trial. A, A 1 s fixation cue. B, A 5 s choice period in which subjects are presented with reward magnitude of the hard task for that trial, and the probability of receiving reward for that trial. C, The 1 s “ready” screen. D, Subjects make rapid button presses to complete the chosen task for 7 s (easy task) or 21 s (hard task). E, Feedback completion of the task. F, Feedback on whether they received any money for that trial.

Figure 2.

Bar graph of changes in mean proportions of HC/HR choices across the placebo, 10 mg of d-amphetamine, and 20 mg of d-amphetamine conditions with SEM error bars (n = 17, in within-subjects design). See Results and Table 2 for inferential statistical data. Post hoc tests conducted depicted as: *p < 0.05, significant pairwise effect of amphetamine doses; **p < 0.05, significant linear effect of amphetamine; ns, not significant. See Results for further information on post hoc tests.