However, preclinical studies suggest that these processes depend on different DA signals. Medications that increase DA increase willingness to exert effort for reward and reward learning, while DA depletion techniques decrease exertion of effort for reward and impair reward learning. Although mesocortical dopamine (DA) is a key neurobiological substrate for reward-based decision-making and learning, it remains unclear how these functions are affected by DAergic medications. Difficulties with these reward-related functions are present in psychiatric disorders including depression, schizophrenia, and addiction. In order to thrive, organisms must choose which rewards to pursue, and must learn from the results of those choices. These results have implications for treatment of neuropsychiatric disorders, which may be characterized by multiple underlying reward dysfunctions. In contrast, d-amphetamine had no significant effect on reward learning. Both baseline effort and working memory emerged as moderators of this effect, such that d-amphetamine increased effort more in individuals with lower working memory and lower baseline effort, also primarily at low to intermediate expected values of reward. Computational modeling analyses suggested this was due to decreased effort discounting rather than probability discounting or decision consistency. ![]() d-Amphetamine increased willingness to exert effort, particularly at low to intermediate expected values of reward. Secondarily, we examined whether the individual characteristics of baseline working memory and willingness to exert effort for reward moderated the effects of d-amphetamine. Participants ( n = 30) completed the Effort Expenditure for Reward Task (EEfRT) measure of effort-related decision-making, and the Probabilistic Reward Task (PRT) measure of reward learning, under placebo and two doses of d-amphetamine (10 mg, and 20 mg). The current study aimed to test the effect of therapeutic doses of d-amphetamine on effort for reward and reward learning in the same healthy volunteers. However, no study has tested how effort and reward learning respond to the same dopaminergic medication within subjects. Therefore, the same dose of a dopaminergic medication could have differential effects on effort for reward vs. Effort-related decision-making and reward learning are both dopamine-dependent, but preclinical research suggests they depend on different dopamine signaling dynamics.
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