SUBSTANTIA-NIGRA D-1 RECEPTORS AND STIMULATION OF STRIATAL CHOLINERGIC INTERNEURONS BY DOPAMINE - A PROPOSED CIRCUIT MECHANISM

Dopamine release can regulate striatal acetylcholine efflux in vivo th rough at least two receptor mechanisms: (1) direct inhibition by dopam ine D-2 receptors on the cholinergic neurons, and (2) excitation initi ated by dopamine D-1 receptors. The neuroanatomical locus of the latte r population of D-1 receptors and the pathway(s) involved in the expre ssion of their influence are controversial issues. We have tested the hypothesis that D-1 receptors in substantia nigra pars reticulata are involved in the excitatory component of dopaminergic actions on striat al acetylcholine output. In vivo microdialysis was used in awake rats. Infusion of the selective D-1 receptor agonist henyl-2,3,4,5-tetrahyd ro-1H-3-benzazepine-7,8-diol (SKF 38393) hydrochloride into pars retic ulata of substantia nigra elicited a significant increase in striatal acetylcholine efflux. Likewise, D-amphetamine applied into pars reticu lata of substantia nigra by reverse dialysis produced an elevation in acetylcholine output measured at a second microdialysis probe in the s triatum. Application of D-amphetamine in the striatum by reverse dialy sis elicited a decrease in striatal acetylcholine efflux that could be reversed subsequently by local application of D-amphetamine in substa ntia nigra pars reticulata. A 2 mg/kg intraperitoneal dose of D-amphet amine, which has no net effect on striatal acetylcholine output under control conditions, elicited a significant decrease in acetylcholine e fflux when the D-1 receptor antagonist ethyl-1-phenyl-2,3,4,5-tetrahyd ro-1H-3-benzazepine (SCH 23390) hydrochloride was applied simultaneous ly via a second microdialysis probe in substantia nigra pars reticulat a. Thus, an excitatory D-1-mediated influence on striatal acetylcholin e output is initiated in substantia nigra pars reticulata, and this in fluence contributes to the effects of indirect dopaminergic agonists s uch as D-amphetamine on striatal acetylcholine efflux. These results i ndicate an important role of somatodendritic dopamine release, in addi tion to nerve terminal dopamine release, in the regulation of activity in basal ganglia circuits.