Dopamine agonists modulate the neural network of reward anticipation in Parkinson's disease patients

Abstract

Dopamine agonists (DA) are widely prescribed to treat Parkinson's disease (PD) but have been found to cause impulse control disorders such as pathological gambling. In a previous study, we found that administration of DA pramipexole in young healthy adults changed the local activity and the connectivity pattern of the nucleus accumbens (NAcc) during reward anticipation. To assess effects of long term DA treatment functional magnetic resonance imaging was used in PD patients in medication-off state (PD-off), the same group of patients in medication-on state (PD-on), and a matched group of healthy controls without medication administration (HC) while they engaged in a reward anticipation task. Compared to HC, PD-off patients showed greater NAcc activity, a stronger interaction between NAcc and the insular cortex, but a weaker interaction between NAcc and the prefrontal cortex. Compared to PD-off, PD-on patients showed less NAcc activity, a weaker insula-striatal connectivity, but a stronger prefrontal-striatal connectivity. The effect of long-term exposure to dopamine agonists thus seems to be different from the effect of short-term medication administration. The change in NAcc activity can be understood in the frame of tonic-phasic dopamine hypothesis. We propose that the imbalance in the connectivity of different reward-related brain areas may underlie the development of pathological gambling in PD patients treated by DA.