How neurodegeneration, dopamine and maladaptive behavioral learning interact to produce impulse control disorders in Parkinson's disease

Impulse control disorders (ICDs) may develop as non-motor adverse effects of dopamine replacement therapy (DRT) in up to 14% of patients with Parkinson's disease (PD). Despite about 10 years of research, several questions are still unanswered about the interaction between DRT and the mesocorticolimbic 'reward' system and the differential response to DRT in a minority of vulnerable patients who develop ICDs. So far, it is not entirely clear how dopamine signaling within the reward system drives decision making and shapes goal-directed behavior. In the present review, we will focus on the physiological role of dopamine in the computation of feedback-related learning signals and incentive salience and how abnormal non-physiological stimulation induced by dopaminergic drugs may interfere with this physiologic signaling in patients with PD as well as in non-parkinsonian subjects with drug addiction. The role of glutamatergic and opioidergic modulation of mesocorticolimbic DA signaling will be discussed. As the management options of ICDs in PD are not entirely satisfactory yet, the sooner we bridge the knowledge gap about the differential abnormal DA transmission within the 'reward' system of vulnerable PD patients with ICDs, the sooner we will find effective treatment strategies.