D-1 RECEPTOR-MEDIATED MODULATION OF THE RELEASE OF GAMMA-AMINOBUTYRIC-ACID BY ENDOGENOUS DOPAMINE IN THE BASAL GANGLIA OF THE RAT

1. Presynaptic D-1 receptors are present on GABAergic terminals of neostriatal projections. 2. By activating these receptors, exogenous dopamine enhances the release of GABA. 3. Here the authors have explored whether endogenous dopamine was also able to activate the receptors, thus enhancing GABA release. 4. The effect of methamphetamine, a dopamine releaser, on the release of tritiated GABA was studied in slices of substantia nigra pars reticulata, entopeduncular nucleus and caudate-putamen, targets of the striatal projections. 5. Methamphetamine enhanced the release of the label. However the enhancement required an intact dopaminergic innervation, since it was lost in slices isolated from rats with 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal system. 6. The activation of the receptors by endogenous dopamine was also judged by the effect of the selective D-1 antagonist SCH 23390 in potassium depolarized slices. By preventing activation of the receptors by dopamine released as result of depolarization, the antagonist reduced GABA release. In 6-OHDA lesioned slices, no reduction was observed, even though the slices were also depolarized 7. The results indicate that endogenous dopamine enhances GABA release from striatal terminals in the pars reticulata of the substantia nigra, entopeduncular nucleus and caudate-putamen. This would facilitate GABAergic neurotransmission. 8. The study suggests that the function of DA in the basal ganglia is widespread, modulating not only the firing of the striatal efferent neurons but also the transmission of the fired impulses across synapses in the target nuclei of these neurons.