6-Hydroxydopamine induced degeneration of noradrenaline neurons in the scorbutic guinea-pig

The effect of the neurotoxic compound 6-hydroxydopamine and its immediate precursor 6-hydroxy-DOPA on noradrenaline uptake and storage in central and peripheral catecholamine neurons of scorbutic and normal guinea-pigs has been investigated. Endogenous noradrenaline in heart and brain as well as the in vitro uptake-accumulation of ³H-noradrenaline in iris and slices of heart and brain were not significantly changed in scorbutic animals. The in vitro formation of ³H-noradrenaline from ³H-dopamine was markedly reduced in heart slices of scorbutic guinea-pigs, due to ascorbic acid being a co-factor for dopamine-β-hydroxylase. There was an increased depletion of brain noradrenaline following tyrosine hydroxylase inhibition produced by α-methyl-p-tyrosine methylester in scorbutic animals, indicating an increased NA turnover. Administration of 6-hydroxydopamine or 6-hydroxy-DOPA resulted in a similar reduction of endogenous NA in brain and heart as well as of the in vitro uptake of ³H-noradrenaline in iris, and slices from heart, cerebral cortex and hypothalamus in scorbutic and control guinea-pigs. These results are discussed in view of current hypotheses on mechanisms involved in the neurotoxic action of 6-hydroxydopamine on catecholamine neurons.