Striatal Dopamine Release During Voluntary Wheel Running

Rodents engage in vigorous running on wheels placed in their cages. This voluntary wheel running (VWR) behavior is used to identify potential neurobiological and genetic factors underlying exercise motivation, with the hope that results will translate to novel strategies to encourage physical activity in humans. However, the translational potential of VWR is limited by a lack of understanding of why rodents engage in VWR. Several hypotheses have been proposed, ranging from foraging to energy balance. An alternative hypothesis is that VWR, like exercise behavior in humans, begins as a goal-directed behavior that over time becomes habitual. The neurobiological substrates underlying goal-directed and habit behavior are well defined. Dopamine release in the dorsomedial striatum (DMS) supports goal-directed behavior, while dopamine release in the dorsolateral striatum (DLS) supports habit. Whether dopamine is released in these specific striatal regions during VWR acquisition and maintenance is unknown. PURPOSE: Here, we test the hypothesis that the acquisition of VWR is associated with dopamine release in the DMS, whereas the long-term maintenance of VWR is associated with dopamine release in the DLS. METHODS: Adult, male and female Long-Evans rats (n = 6 per sex) were implanted with guide cannulae aimed at the DMS or DLS. After 4 days and 3 weeks of VWR, a carbon-fiber electrode was inserted into the guide cannulae and dopamine release events during running and non-running epochs were measured with fast-scan cyclic voltammetry. RESULTS: After 4 days of VWR, dopamine release was greater during running compared to non-running in the male DMS (1.27 ± 0.24 nA vs. 0.12 ± 0.1 nA; p < 0.05), but not DLS (1.42 ± 0.34 nA vs. 1.14 ± 0.3 nA; p > 0.05). Analysis of dopamine release in the DLS and at the 3 week timepoint in both sexes is ongoing. CONCLUSIONS: Since DMS dopamine drives goal-directed behavior, data are consistent with the onset of VWR being goal-directed and mediated by dopamine in the DMS. Analysis of DLS dopamine will provide insight into whether VWR becomes habitual. Results could have important implications for the translational potential of VWR as a pre-clinical model for the study exercise motivation. This study represents the first time that dopamine release has been measured in the brain during VWR in rodents. NIHR01MH125898