Intracisternal dose-response analysis of 6-hydroxydopamine-induced noradrenergic sprouting in the neonatal rat cerebellum.

The dose-response relationship between neonatal 6-hydroxydopamine and noradrenergic regenerative sprouting in the cerebellum was characterized by using intracisternal doses of 10 to 80 micrograms of the drug. Noradrenergic regeneration was assessed in seven subregions of the cerebellum by measurement of norepinephrine (NE) levels once the rats were one-month-old. Regenerative sprouting occurred to a significant extent at drug doses between 10 to 40 micrograms, with peak NE elevations occurring after a 20-microgram dose. Recovery of NE was not uniform throughout the cerebellum but was maximal in the anterior vermis and minimal in the posterior vermis. An 80-microgram dose produced near total loss of cerebellar NE. This is contrasted to the cerebral cortical noradrenergic innervation which responded with significant long-term degeneration to a dose as low as 10 micrograms. In both areas, the initial effect of the drug treatment was to reduce NE levels by 95% or more. A couple of conclusions can be made. The magnitude of the difference between the cerebellar and cerebral cortical dose-response relationships is consistent with a regenerative mechanism subserving the recovery of NE in the cerebellum. Secondly, the increase of NE in the cerebellum is reciprocally related to destruction of the forebrain noradrenergic projection.