Changes in the development of central noradrenaline neurones following neonatal administration of 6-hydroxydopamine.

Abstract

Abstract— The effects of the neurotoxic compound 6‐hydroxydopamine on central noradrenaline (NA) neurones have been investigated in the adult rat after systemic administration of the drug at birth. This treatment produced a permanent and selective reduction in endogenous noradrenaline, [3H]noradrenaline uptake in vitro and the number of histochemically demonstrable noradrenaline nerve terminals in the forebrain, certainly related to neuroneal degeneration. The fluorescence morphology of the noradrenaline perikarya in the locus coeruleus was not notably affected. In the pons‐medulla region, the 6‐hydroxydopamine treatment led to an almost two‐fold increase in endogenous noradrenaline with a similar increase in [3H]noradrenaline uptake and formation of 3H‐catecholamines from [3H]tyrosine. Fluorescence histochemistry revealed an increased number of noradrenaline nerve terminals which in addition showed an increased fluorescence intensity. Subcellular distribution studies of endogenous noradrenaline in pons—medulla disclosed the highest relative noradrenaline increase in the microsomal fraction after 6‐hydroxydopamine at birth. Sucrose gradient centrifugations disclosed that the pons‐medulla synaptosomes from 6‐OH‐DA treated rats sedimented at a higher sucrose concentration than those from untreated controls. It is concluded that treatment of neonate rats with 6‐hydroxydopamine produces a selective degeneration of noradrenaline nerve terminals in the forebrain, especially in the cerebral cortex, whereas in the pons‐medulla this treatment leads to an increased intraneuronal noradrenaline concentration due to accumulation of noradrenaline in collateral systems not affected by 6‐hydroxydopamine and probably also to an increased outgrowth of noradrenaline nerve terminals.