Functional anatomical and behavioral consequences of dopamine receptor stimulation.

Abstract

Taken together with electrophysiological data, these results suggest that in states of DA deficiency, systemically administered L-dopa or DA agonist drugs inhibit cell firing in the major output nuclei of the basal ganglia (GPI and SNPR). We propose that DA produces this net effect by a direct influence on the striato-GPI and striato-SNPR neurons, as well as indirectly via the striato-GPE-STN-GPI/SNPR circuit. The RCGU data suggest that DA activates the direct pathway by stimulating D1 receptor-bearing striatal GABAergic neurons projecting to GPI and SNPR. Supportive evidence includes the ability of D1 agonists to facilitate GABA release in the striatum and to increase the firing rates of striatonigral neurons. The RCGU data also support a net stimulatory action of DA on the GPE output on STN, consistent with the excitatory effects of DA on GPE neuronal firing rates. This effect may be mediated by both D1 and D2 receptors. Stimulation of this pathway should physiologically inhibit the STN resulting in dysfacilitation of the GPI and SNPR. According to this scheme, DA exerts complementary actions via both direct and indirect anatomical pathways to decrease tonic firing rates of intrinsic neurons in the major output nuclei of the basal ganglia (i.e., GPI and SNPR).