Dopamine receptor alterations correlate with increased GABA levels in adult rat neostriatum : effects of a neonatal 6-hydroxydopamine denervation

Abstract The effects of neonatal intracerebroventricular 6-hydroxydopamine (6-OHDA) injection on the densities of dopamine (DA) receptors and GABA levels were determined in the rostral neostriatum of adult rats. Measurement of GABA turnover indicated that increased tissue GABA in the DA-lesioned neostriatum is a consequence of higher GABA synthesis rate (205%). Binding experiments with [ 3 H]SCH23390 (D 1 receptors) and [ 3 H]raclopride (D 2 receptors) point to a correlation between tissue GABA content and altered DA receptors. Three months after the lesion there was a 27% decrease in D 1 receptors and a 22% increase in D 2 receptors. In control neostriatum, GABA levels were inversely related to D 2 receptors and this relationship was reversed after 6-OHDA treatment. In contrast, the positive correlation between GABA and D 1 receptors remained unchanged after the lesion. Irreversible blockade of DA receptors by N -ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) decreased both D 1 and D 2 sites (73–87%) in both control and lesioned neostriatum, but increased GABA levels by 25% only in animals which have received 6-OHDA just after birth. Following acute inhibition of DA synthesis or of DA catabolism, GABA levels remained unchanged. The present results indicate that DA depletion by itself is not the cause for the increase in GABA levels. The augmented GABAergic activity following neonatal 6-OHDA is seemingly influenced primarily by DA receptor status; presumably, changes in D 2 receptor properties during maturation may be a principal cause for an increase in neostriatal GABA content.