Background:~The dopamine receptor agonist pramipexole has recently been suggested as a potential novel antidepressant drug. While preliminary clinical data hint at its efficacy in treating depressive symptoms, our current understanding of its impact on neurocognitive processes is relatively limited. This is in part because, so far, mechanistic studies have largely focused on the effects of single-dose treatments. However acute administration of dopaminergic drugs likely has different cognitive effects than the more prolonged administration that is used clinically.~Aim of study:~To explore and characterise the effects of a 12 to 15 day regime of pramipexole on behavioural and neural measures of reward learning, emotional information processing, motivational invigoration, and subjective experience.~Methods:~Using a double-blind, parallel-group design, forty healthy volunteers (male and female, aged 18 to 45 years) will be randomly allocated to a 12 to 15 day regime of either pramipexole (maximum daily dose of 1.0 mg pramipexole salt) or placebo. At baseline and after 12 to 15 days of treatment, a set of previously established cognitive tasks and questionnaires tapping into reward learning, emotional information processing, motivational invigoration and subjective experience will be administered. Furthermore, at 12 to 15 days of treatment, all participants will undergo functional magnetic resonance imaging to compare neural responses to reward- and emotion-related information.~Hypotheses:~Our working hypothesis is that pramipexole will enhance reward sensitivity, motivational invigoration and hedonic experience and might positively bias emotional information processing.~Implications:~This will be the first study to broadly explore and characterise the neurocognitive effects of pramipexole administered for a clinically relevant time period. The results of the study will add to our understanding of the cognitive mechanisms through which pramipexole could exert both its beneficial as well as its adverse clinical effects.
The dopamine agonist pramipexole has recently been suggested as a potential novel antidepressant drug. While preliminary clinical data hint at its efficacy in treating depressive symptoms, our current understanding of its impact on neurocognitive processes is relatively limited. This is in part because mechanistic studies have largely focused on the effects of single-dose treatments. However, such acute administration of dopaminergic drugs likely has different cognitive effects than the more prolonged administration that is used clinically. This study therefore aims to explore and characterise the neurocognitive effects of more prolonged pramipexole treatment. Forty healthy volunteers will be randomly allocated to 12 to 15 days of treatment with either pramipexole or placebo. Study participants as well as researchers will be blinded as to which treatment is used. Before and after treatment all participants will perform a set of psychological tasks and questionnaires evaluating reward-based learning, emotional information processing, motivational vigour and subjective experience. Furthermore, functional magnetic resonance imaging (fMRI) will be used to compare neural activity during emotion and reward processing between the two treatment groups. We hypothesises that pramipexole might enhance reward sensitivity, motivational vigour, and pleasure experience and could induce positive biases in emotional information processing.