Regional changes in [3H]-noradrenaline uptake, catecholamines and catecholamine synthetic and catabolic enzymes in rat brain following neonatal 6-hydroxydopamine treatment

Abstract

6-Hydroxydopamine (6-OH-DA) treatment of rats at birth (with the analyses conducted in the adult stage) produced marked regional variations in changes in endogenous noradrenaline (NA) and [3H]NA uptake in the CNS. The most pronounced reductions were seen in the cerebral cortex, hippocampus and the spinal cord. Moderate changes or none at all were seen in the hypothalamus, septum and thalamus. Marked increases in endogenous NA and [3H]NA uptake were seen in the mesencephalon and the pons-medulla oblongata. There was in general a close correlation between the changes in endogenous NA and [3H]NA uptake. The results from the cerebellum varied, depending on the developmental stage at which the 6-OH-DA treatment was performed. 6-OH-DA treatment up to three days after birth generally led to a marked increase in both endogenous NA and [3H]NA uptake, while continuing the treatment caused a marked reduction of both parameters. The 6-OH-DA treatment caused no changes in endogenous dopamine (DA) in all regions analysed. Enzyme activity assays showed that DA-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) were greatly reduced in the cerebral cortex, while the activity of both enzymes was almost double in the pons-medulla. No changes in the activity of phenylethanol-amine N-methyltransferase (PNMT), DOPA decarboxylase, COMT and MAO were seen after 6-OH-DA at birth. Measurements of choline acetyltransferase activity displayed only minute changes. The present results strongly support the view that 6-OH-DA treatment in the neonate stage produces a very selective action on NA neurones belonging to the locus coeruleus system from a structural standpoint, leaving DA- and PNMT-containing neurones unaffected. [3H]NA uptake in whole CNS was almost unchanged, despite the marked regional variations. The results have been interpreted as being due to a 'pruning effect', where the permanent NA denervation in distant nerve terminal projections (e.g. cerebral cortex) leads to a compensatory sprouting and increased outgrowth of NA terminal projections in areas close to the perikarya (e.g. pons-medulla). Furthermore, the results support the view that the growing locus coeruleus neurones are strictly programmed to produce a certain quantity of nerve terminal volume and arborization during the postnatal development.