Time course of the effects of 6-hydroxydopamine on catecholamine-containing neurones in rat hypothalamus and striatum.

1. The effects of intraventricular injection of 6-hydroxydopamine (6-OHDA) on tyrosine hydroxylase activity, uptake of (3)H-noradrenaline and endogenous catecholamine concentration in rat hypothalamus and striatum were investigated at various times after the injection of 6-OHDA.2. In the hypothalamus after the injection of 250 mug of 6-OHDA there was a rapid decrease in tyrosine hydroxylase activity, (3)H-noradrenaline uptake and noradrenaline content, which was essentially complete within 2 hours.3. In the striatum after this dose of 6-OHDA there was a much slower reduction in tyrosine hydroxylase activity and (3)H-noradrenaline uptake during the first 48 h after drug injection. For the first 24 h the dopamine concentration in this brain area was increased significantly above control values, but had fallen below control values by 48 hours.4. After the injection of a smaller dose of 6-OHDA (25 mug) the only detectable change in the striatum was a rapid increase in the dopamine concentration. In the hypothalamus this dose induced a rapid depletion of noradrenaline, not accompanied initially by any significant reduction in tyrosine hydroxylase activity.5. These results are consistent with the hypothesis that 6-OHDA causes a rapid degeneration of catecholamine-containing nerve terminals in the central nervous system (CNS). These degenerative changes, indicated by the loss of tyrosine hydroxylase and noradrenaline uptake sites, did not appear to be preceded by an initial displacement of endogenous catecholamines by 6-OHDA, except possibly at early times after the administration of small doses of the drug.