Exercise Leads to Brain Glucose Metabolism Activation, Increased Dopamine D1 Receptor Levels and is Negatively Correlated with Social Behavior.

Background: Exercise enhances overall health, playing an important role in protecting against diseases that impact brain function. Studies show that physical activity influences several key biological processes, including dopamine signaling, brain glucose metabolism (BGluM), and social behavior.

Methods: Male sedentary and chronic exercise rats were examined for dopamine signaling and social behavior. Tyrosine hydroxylase (TH) immunohistochemistry (IHC), and D1 and D2 receptor (D1R and D2R) autoradiography was used to assess dopamine signaling; [18F]-Fluorodeoxyglucose positron emission tomography (FDG PET) was used to measure brain functional connectivity; Crawley's three-chamber sociability test was used to measure social behavior; and Pearson correlation was used to analyze correlations between social interaction and TH, D1R, and D2R binding.

Results: Exercised rats demonstrated greater D1R binding within several regions of the caudate putamen and nucleus accumbens. PET image analysis showed significantly higher BGluM in the exercised rats compared with the sedentary controls across several brain regions. These regions are associated with enhanced functional connectivity related to movement, olfaction, cardiovascular function, and predator awareness. Exercise had no significant effect on social interaction. Pearson correlation analysis revealed a significant negative relationship between social interaction and D1R binding.

Conclusions: Chronic aerobic exercise did not significantly alter social interaction, TH, or D2R binding. D1R binding was enhanced in the exercise group compared with the sedentary group and was negatively correlated with social interaction. We speculate that approach behavior was attenuated by exercise due to social threat stimulation. Functional connectivity imaging data showed significant glucose metabolic activation within the cuneiform nucleus, which has been previously shown to be critical in defensive behavior. This may explain the lack of significant effect of exercise on approach or exploratory behavior. These findings support the potential of exercise in response to social behavior and the possible attenuation of social behavior towards a social threat or socially inappropriate behavior. Exercise can induce metabolic transience that may assist rats in detecting odors from larger predatory animals.