Abstract
Treatment with the dopamine D2/D3 receptor agonist pramipexole has demonstrated promising clinical effects in patients with depression. However, the mechanisms through which pramipexole might alleviate depressive symptoms are currently not well understood. Conventional antidepressant drugs are thought to work by biasing the processing of emotional information in favour of positive relative to negative appraisal. In this study, we used an established experimental medicine assay to explore whether pramipexole treatment might have a similar effect. Employing a double-blind, parallel-group design, 40 healthy volunteers (aged 18 to 43 years, 50% female) were randomly allocated to 12 to 15 days of treatment with either pramipexole (at a peak daily dose of 1.0 mg pramipexole salt) or placebo. After treatment was established, emotional information processing was assessed on the neural level by measuring amygdala activity in response to positive and negative facial emotional expressions, using functional magnetic resonance imaging (MRI). In addition, behavioural measures of emotional information processing were collected at baseline and on drug, using an established computerized task battery, tapping into different cognitive domains. As predicted, pramipexole-treated participants, compared to those receiving placebo, showed decreased neural activity in response to negative (fearful) vs. positive (happy) facial expressions in bilateral amygdala. Contrary to our predictions, however, pramipexole treatment had no significant antidepressant-like effect on behavioural measures of emotional processing. This study provides the first experimental evidence that subacute pramipexole treatment in healthy volunteers modifies neural responses to emotional information in a manner that resembles the effects of conventional antidepressant drugs.
Highlights
Depression is considered a leading cause of disability worldwide
This study explored the effects of subacute treatment with the dopamine D2 receptor agonist pramipexole on neural and behavioural measures of emotional information processing
Contrary to our predictions, there was no effect of pramipexole on behavioural measures of emotional information processing
Summary
Depression is considered a leading cause of disability worldwide. various medications have shown clinical efficacy in this condition [1], a considerable number of patients do not experience sufficient symptom improvement following conventional antidepressant treatment, even when multiple therapeutic attempts are made [2]. One agent that has received attention in this specific context recently is the non-ergot dopamine agonist pramipexole [2,5]. This drug shows selective affinity for and full intrinsic activity at the dopamine D2 receptor subfamily, the D3 receptor, which is found in high concentration in mesolimbic areas implicated in mental processes related to emotion and mood [5,6]. In a recent meta-analysis, including 504 patients with major depressive episodes in total, it was found that pramipexole treatment was associated in the short-term with a response rate of 52.2% and a remission rate of 36.1% [5]. Focusing on the long-term effects, these numbers increased to a 62.1% response rate and a 39.6% remission rate [5]
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