BOTH DOPAMINE D1 AND D2 RECEPTOR ANTAGONISM RESULTED IN SIMILAR MOTOR IMPAIRMENTS, BUT THE EFFECTS ON NEURAL ACTIVITY WERE DIFFERENT

The striatum has two types of projection neurons: Direct pathway neurons express the dopamine D1 receptor (D1R); indirect pathway neurons express the D2 receptor (D2R). D1R activation is thought to enhance neuronal activity, and D2R activation to suppress it. However, how these receptors influence neural activity and behavior at the whole-brain level remains unclear. To elucidate the roles of D1R andD2R on the neural activity and motor function, we conducted behavioral experiments using mice administered with either a D1R or D2R antagonist, while simultaneously recording whole-brain neural activity. Akinesia was evaluated using the catalepsy test, and spontaneous locomotor activity and anxiety-like behavior were assessed using the open field test. Administration of either antagonist resulted in increased catalepsy and reduced spontaneous locomotor activity, while no anxiety-like behavior was observed. Whole-brain neural activity was measured using quantitative activation-induced manganese-enhanced MRI (qAIM-MRI). Mn²⁺ enter neurons through voltage-dependent calcium channels and preferentially accumulate in highly active neurons. Because Mn²⁺ shortens the longitudinal relaxation time, qAIM-MRI enables quantification of the history of neural activity in freely moving subjects. D1R antagonist administration increased neural activity in the striatum, external segment of the globus pallidus, and substantia nigra pars reticulata, while decreasing activity in the thalamus. In contrast, D2R antagonist administration reduced neural activity across multiple regions, including the striatum, globus pallidus, and thalamus. These findings were different from the conventional view regarding changes in neural activity associated with dopamine receptor activation. Further studies are required to clarify the relation among dopamine, neuronal activity, and motor function.