Role of dopamine in flexible behaviour

The ability to adapt flexibly to our constantly changing environment requires
cognitive and motivational control processes. These control processes implicate
the brain substance dopamine. A variety of neuropsychiatric disorders,
characterized by maladaptive behaviour, are treated with dopamine-enhancing
drugs. However, there is large individual variation in dopaminergic drug
efficacy. In addition, dopaminergic drugs can have contrasting effects across
different task demands, so that some task benefit while other tasks are
impaired by the same dopaminergic drug. The present project consists of four
experiments in which we investigate the mechanisms underlying this large
variability in dopaminergic drug efficacy. this work is essential for the
understanding of the neurobiological of adaptive behaviour, but also for the
development of pharmacotherapy that is targeted at specific behavioural
deficits as well as at specific individuals.

• Identify regional specificity of dopaminergic drug effects, i.e. the distinct
behavioural roles of dopamine in the striatum and dopamine in the prefrontal
cortex.
• Identify receptor specificity of dopaminergic drug effects, i.e. the distinct
behavioural roles of dopaminergic activity at D1 family receptors and at D2
family receptors
• Identify neurobiological and genetic basis of individual variability in
dopaminergic drug effects

Each subject will be tested in a cross-over design which consists of two or
four visits. On each visit the subject is administered a single dose of
bromocriptine (1.25mg), sulpiride (400mg) and/or placebo. Approximately 2 hours
after administration, subjects will enter the fMRI scanner for 1 hour, to
visualize region- and task-specific brain activity. After scanning, they will
complete a relatively standard neuropsychological test battery.

Subjects will be administered the following oral capsules for intake, each on a
different visit: 1.25mg bromocriptine, 400mg sulpiride, 100mg levodopa + 25mg
carbidopa and placebo.

Participation is without health risk. The burden on subjects consists of
time-investment (max 21 hours spread over 4 visits) and the possible
discomfort of self-report questionnaires, blood sampling, capsule intake,
drug-induced but transient nausea, noise and claustrophobia of MRI scans,
restrictions of diet, alcohol or other drug-intake prior to the test session.