Dopamine Receptor Function in the Basal Ganglia

Clinical disorders that affect the basal ganglia, such as Parkinson's disease, are believed to result from an imbalance in the activity of the two main output pathways of the striatum, the direct and indirect striatal output pathways. Dopamine (DA) modulates the activity of these pathways through the select distribution of the D1 and D2 DA-receptor subtypes on neurons, which give rise to the direct and indirect striatal output pathways, respectively. Studies employing quantitative in situ hybridization histochemistry have been used to analyze changes in levels of gene-regulated peptides and immediate early genes in direct and indirect striatal output neurons in response to selective D1- and D2-agonist treatments. D2-receptor activation reverses and D1-receptor activation increases gene regulation in indirect and direct striatal output neurons, respectively. These findings suggest that functional activity in the two output pathways of the striatum are oppositely regulated by DA by segregation of the D1- and D2-receptor subtypes on different striatal neuron populations. A proposed pharmacologic strategy for the treatment of Parkinson's disease based on these findings is suggested.