Pramipexole is widely prescribed to treat Parkinson's disease. It has been found to cause impulse control disorders such as pathological gambling. To examine how pramipexole modulates the network of reward anticipation, we carried out a pharmacological functional magnetic resonance imaging study with a double-blind, within-subject design. During the anticipation of monetary rewards, pramipexole increased the activity of the nucleus accumbens (NAcc), enhanced the interaction between the NAcc and the anterior insula, but weakened the interaction between the NAcc and the prefrontal cortex. These results suggest that pramipexole may exaggerate incentive and affective responses to possible rewards, but reduce the top-down control of impulses, leading to an increase in impulsive behaviors. This imbalance between the prefrontal-striatum connectivity and the insula-striatum connectivity may represent the neural mechanism of pathological gambling caused by pramipexole. Hum Brain Mapp, 2011. © 2010 Wiley-Liss, Inc.