Dopamine and Cognition
Condition: Sulpiride's Effect on Striatal BOLD Signal During Working Memory Gating; Interaction of Sulpiride, Average Reward Rate and Evidence Accumulation; Interaction of Sulpiride, Average Reward Rate and Cognitive Effort
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      A more detailed description can be found in the approved research protocol as well as the
      pre-registrations. The links to the pre-registrations will be made available upon
      publication.
    

Intervention name(s): Sulpiride 400 MG; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): All participants will receive one single dose of 400mg sulpiride. None of the participants will receive repeated doses. In order for the fMRI data acquisition to coincide with the time-window of maximal drug effects represented by a combination of plasma kinetics and physiological effects we will administer the drug 90 minutes prior to fMRI data acquisition.; All participants will receive placebo during one of the sessions.
Other intervention name(s): Dogmatil
Intervention MeSH terms: Sulpiride
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a within-subjects (i.e., crossover), double-blind, randomized placebo-controlled study.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science