Dopamine released from mesencephalic transplants restores modulation of striatal acetylcholine release after neonatal 6-hydroxydopamine: an in vitro analysis.

After chemical lesions which destroy the nigrostriatal dopamine pathway, transplants rich in dopamine neurons innervate the striatum and, with appropriate stimulation, drive host motor behaviors normally mediated by dopamine. We wished to determine whether dopamine released from the transplant also reinstated dopaminergic inhibition of striatal acetylcholine release. Three-day-old rat pups received bilateral intraventricular injections of 6-hydroxydopamine. Three days later cell suspensions prepared form embryonic ventral mesencephalon were injected unilaterally into the striatum. Tail pinch and amphetamine were able to elicit contralateral turning in many of these animals. Only those animals which rotated greater than or equal to 5 turns/min were included for further analysis. Subsequent assays indicated that 6-hydroxydopamine had depleted striatal dopamine to 4% of control and that the transplant had increased dopamine levels to 11% of control. Superfused striatal slices were stimulated (8 Hz, 1 min) and then exposed to amphetamine (10 microM, 3 min). The slice released dopamine, as measured by HPLC, and acetylcholine, as measured by tritium efflux after preincubation with [3H]choline. Moreover, the release of acetylcholine was inhibited by endogenous dopamine as indicated by the ability of sulpiride (1 microM) to increase tritium efflux. Striatal slices prepared from lesioned animals showed a reduction in dopamine overflow in response to both electrical stimulation (0.6% of control) and amphetamine (1% of control), and a decrease in the ability of sulpiride to increase electrically evoked acetylcholine overflow (12% of control). Transplantation partially restored the dopaminergic response to electrical stimulation (21% of control), and amphetamine (15% of control) and fully restored the sulpiride-induced increase in acetylcholine overflow (98% of control).(ABSTRACT TRUNCATED AT 250 WORDS)