Control of the Neurotoxicity of 6-Hydroxydopamine by Intraneuronal Noradrenaline in Rat Iris

Abstract

In vitro studies with the neurotoxic compounds 6‐hydroxydopamine (6‐OH‐DA) and 6‐aminodopamine (6‐A‐DA) showed that noradrenaline (NA) markedly inhibited the autooxidation of 6‐OH‐DA, but not of 6‐A‐DA. In vivo studies of the adrenergic nerves in rat iris showed that the neurotoxic potency of 6‐OH‐DA, but not 6‐A‐DA, was increased after NA depletion by α‐methyl‐p‐tyrosine methylester(H44/68). Neurotoxicity was evaluated by measuring the associated decrease in ³H‐NA uptake. lntraocular injection of NA counteracted the degenerative action of 6‐OH‐DA in both untreated and H44168 pretreated rats. Intraocular NA did not interfere with the neurotoxicity of 6‐A‐DA. Additionally, octopamine did not affect the rate of autooxidation nor the neurotoxic potency of 6‐OH‐DA or 6‐A‐DA. Control experiments with ³H‐6‐OH‐DA showed that the intraneuronal NA levels did not significantly affect the intraneuronal accumulation of 6‐OH‐DA. The parallelism between the in vitro results on autooxidation and in vivo data on neurotoxicity makes it appear that the neurotoxic potency of 6‐OH‐DA and 6‐A‐DA is closely associated with their rates of autooxidation. The control of the degenerative action of 6‐OH‐DA by intraneuronal NA may be mediated via reaction of NA with radicals formed from oxygen during autooxidation of 6‐OH‐DA.