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.
Phase:
N/A
Details
Lead Sponsor:
Donders Centre for Cognitive Neuroimaging
Collaborators:
Dr. Hanneke den Ouden, Donders Centre for Cognition, Radboud University Dr. Rebecca Calcott, Donders Centre for Cognitive Neuroimaging, Radboud University Floortje Spronkers, Donders Centre for Cognition, Radboud University Funding: NWO + KNAW Prof. Dr. Robbert-Jan Verkes, Radboud University Medical Centre Department of Psychiatry