DOPAMINE-RECEPTOR ALTERATIONS CORRELATE WITH INCREASED GABA LEVELS INADULT-RAT NEOSTRIATUM - EFFECTS OF A NEONATAL 6-HYDROXYDOPAMINE DENERVATION

The effects of neonatal intracerebroventricular 6-hydroxydopamine (6-O HDA) injection on the densities of dopamine (DA) receptors and GABA le vels were determined in the rostral neostriatum of adult rats. Measure ment of GABA turnover indicated that increased tissue GABA in the DA-l esioned neostriatum is a consequence of higher GABA synthesis rate (20 5%). Binding experiments with [H-3]SCH23390 (D-1 receptors) and [H-3]r aclopride (D-2 receptors) point to a correlation between tissue GABA c ontent and altered DA receptors. Three months after the lesion there w as a 27% decrease in D-2 receptors and a 22% increase in D-2 receptors . In control neostriatum, GABA levels were inversely related to D-2 re ceptors and this relationship was reversed after 6-OHDA treatment. In contrast, the positive correlation between GABA and D-1 receptors rema ined unchanged after the lesion. Irreversible blockade of DA receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) decreased bo th 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 o r of DA catabolism, GABA levels remained unchanged. The present result s indicate that DA depletion by itself is not the cause for the increa se in GABA levels. The augmented GABAergic activity following neonatal 6-OHDA is seemingly influenced primarily by DA receptor status; presu mably, changes in D-2 receptor properties during maturation may be a p rincipal cause for an increase in neostriatal GABA content.