Baseline dopamine predicts individual variation in methylphenidate’s effects on cognitive motivation

Contrasting cognitive effects of dopaminergic drugs, for example in low- and high-impulsive individuals, have long been argued to reflect variability in baseline levels of dopamine. Here, we investigated whether individual differences in the effects of methylphenidate on cognitive motivation depend on baseline dopamine synthesis capacity. Fifty healthy participants (25 women) underwent an [F]DOPA PET scan to quantify baseline dopamine synthesis capacity. They performed an effortful working memory task prior to drug administration and a cognitive effort discounting task after drug administration. To examine the neurochemical specificity to dopamine, effects of methylphenidate were compared with those of the selective dopamine D2 receptor antagonist sulpiride. Participants also completed a questionnaire to assess trait impulsivity. Methylphenidate increased cognitive motivation to a greater extent in people with high baseline midbrain dopamine synthesis capacity than in people with low baseline midbrain dopamine. Parallel effects were observed as a function of trait impulsivity, with high-impulsive participants exhibiting greater motivational enhancing effects than low-impulsive participants. This effect was fully mediated by baseline dopamine. There were no significant effects of sulpiride. This study provides a link between motivational enhancement by methylphenidate, baseline dopamine and trait impulsivity, thereby advancing the biological understanding of individual variation in the effects of methylphenidate.