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

Hofmans, L.; Papadopetraki, D.; van den Bosch, R.; Määttä, J. I.; Froböse, M. I.; Zandbelt, B. B.; Westbrook, A.; Verkes, R.-J.; Cools, R.

2019-11-29 neuroscience
10.1101/859637 bioRxiv
Show abstract

The cognitive enhancing effects of methylphenidate are well established, but the mechanisms remain unclear. We recently demonstrated that methylphenidate boosts cognitive motivation by enhancing the weight on the benefits of a cognitive task in a manner that depended on striatal dopamine. Here we considered the complementary hypothesis that methylphenidate might also act by changing the weight on the opportunity cost of a cognitive task. To this end, fifty healthy participants (25 women) completed a novel cognitive effort discounting task that was sensitive to opportunity cost, and required choices between task and leisure. They were tested on methylphenidate, sulpiride or placebo and also underwent an [18F]DOPA PET scan to quantify baseline dopamine synthesis capacity. Methylphenidate boosted choices of cognitive effort over leisure across the group, and this effect was greatest in participants with more striatal dopamine at baseline. The effects of sulpiride did not reach significance. This study strengthens the motivational account of methylphenidates effects on cognition and suggests that methylphenidate reduces the cost of mental labor by increasing striatal dopamine.

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