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The purpose of the current study was to examine changes in dopamine D2 receptor (DA‐D2R) expression within the basal ganglia of MPTP mice subjected to intensive treadmill exercise. Using Western immunoblotting analysis of synaptoneurosomes and in vivo positron emission tomography (PET) imaging employing the DA‐D2R specific ligand [¹⁸F]fallypride, we found that high intensity treadmill exercise led to an increase in striatal DA‐D2R expression that was most pronounced in MPTP compared to saline treated mice. Exercise‐induced changes in the DA‐D2R in the dopamine‐depleted basal ganglia are consistent with the potential role of this receptor in modulating medium spiny neurons (MSNs) function and behavioral recovery. Importantly, findings from this study support the rationale for using PET imaging with [¹⁸F]fallypride to examine DA‐D2R changes in individuals with Parkinson's Disease (PD …