L-DOPA inhibits depolarization-induced [3H]GABA release in the dopamine-denervated globus pallidus of the rat: the effect is dopamine independent and mediated by D2-like receptors

The effect of L-DOPA on [3H]GABA release in slices of globus pallidus from 6-OHDA-lesioned rats was studied. Release was evoked by high (15 mM) K+. The lesion reduced dopamine content and dopamine synthesized from L-DOPA. The inhibition of DOPA decarboxylase blocked dopamine synthesis. Endogenous dopamine released by high K+ inhibited [3H]GABA release in normal but not in lesioned slices. L-DOPA inhibited (IC50 = 0.44 µM) evoked [3H]GABA release. The inhibition was via D2-like receptors but not mediated by dopamine. The turning behavior induced by L-DOPA methyl ester (25 mg/kg, i.p.) was not abolished by the DOPA decarboxylase inhibitor 3-hydroxybenzylhydrazine but in this condition it was abolished by sulpiride. Results suggest that L-DOPA acting as D2-like agonist inhibits GABA release in the rat globus pallidus and induces turning behavior in rats with unilateral lesions of the dopamine innervation. L-DOPA could control Parkinson’s disease symptoms acting not only as dopamine precursor but also by itself.