Dopamine and Cognition

Rationale: To unravel the role of dopamine in gating of working memory, motivation and learning. Objective: The primary objective of this study is to isolate effects of blocking D2 receptor stimulation on gating of working memory, reinforcement learning and reward-based motivation, and their associated physiological changes (measured with fMRI and eye tracking). The secondary objective is to assess the degree to which the effects of D2 receptor action vary as a function of proxy measures of baseline dopamine levels. Study design: A double-blind placebo controlled within-subject design will be employed, in which young healthy participants are tested twice, once on placebo, and once on a low oral dose (400mg) of the D2 receptor antagonist sulpiride. This design and drug dose is commonly used in our lab without side effects (previously approved CMO protocols 2011/204, 2008/078 \& 2016/2646). Study population: Healthy human participants, 18 - 45 yr old. We will recruit 46 participants. Intervention: Participants will receive both 400 mg sulpiride and placebo, in separate sessions in a counterbalanced order. Main study parameters/endpoints: BOLD signal measured with fMRI, and behavioural performance on cognitive tasks. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will attend 3 study sessions: A screening session and 2 pharmaco-fMRI sessions (sulpiride and placebo). Participants will complete a baseline battery of tasks and questionnaires, a structural MRI scan, as well as a battery of tasks both in and outside the scanner. On the day preceding each pharmaco-fMRI session, participants will have to adhere to some simple restrictions with respect to medication, alcohol and drug intake. On the day of testing participants will have to refrain from smoking and stimulant-containing drinks. Sulpiride can be administered safely without any relevant risk of serious adverse events and has been approved for clinical use in the Netherlands.