Unilateral accumbal dopamine depletion affects decision-making in a side-specific manner

Mechanisms underlying affective and cognitive deficits in Parkinson's disease (PD) remain less studied than motor symptoms. Nucleus accumbens (NAc) is affected in PD and due to its well-known involvement in motivation is an interesting target in this context. Furthermore, PD is frequently asymmetrical, with side-specific deficits aligning with evidences of accumbal laterality. We therefore used a 6-hydroxydopamine (6-OHDA) model to study the role of left and right NAc dopamine depletion in a battery of behavioral tasks. 2 months old male rats were used in all experiments. Habitual-based and goal-directed decision-making, impulsivity, anxiety- and depressive-like behavior and motor performance were tested 3 weeks after left (6-OHDA L) or right (6-OHDA R) NAc lesion was induced. Upon contingency degradation, 6-OHDA R decrease their lever press rate less than Sham and 6-OHDA L, indicating an impairment in the shift from habit-based to goal-directed strategies. On the other hand, 6-OHDA L lesions lead to increased rates of premature responding when delays where increased in the variable delay-to-signal test. Importantly, in both paradigms task acquisition was similar between groups. In the same line we found no differences in the amount of sugared pellets eaten when freely available as well as in both general and fine motor behaviors. In conclusion, left and right NAc play distinct roles in the contingency degradation and impulsivity. More studies are needed to understand the mechanisms behind this functional lateralization and its implications for PD patients.