Resistance of central phenylethanolamine-n-methyl transferase containing neurons to 6-hydroxydopamine

The effects of the catecholamine neurotoxin 6-hydroxydopamine on phenylethanolamine-N-methyl transferase (PNMT) in rat brain has been investigated by biochemical and immunohistochemical analysis. 6-Hydroxydopamine was administerered either intracisternally to adult rats or systemically to newborn rats, treatments known to affect markedly central noradrenaline neurons. None of these treatments had any significant effect on the PNMT activity in the hypothalamus, pons-medulla and the spinal cord, as measured in vitro using a radiometric assay. The neonatal 6-hydroxydopamine treatment, which produced an almost complete noradrenaline denervation in the spinal cord, had no notable effect on the specific PNMT immunofluorescence localized in nerve terminals in the spinal cord. Transection of the spinal cord led to an almost complete disappearance of the PNMT activity and the specific immunofluorescence below the transection, pointing to the existence of a descending PNMT containing pathyway in the spinal cord. The present results show that the PNMT neurons are resistant to the neurotoxic action of 6-hydroxydopamine, possibly due to lack of catecholamine uptake mechanism or due to these neurons having an uptake mechanism with a low affinity for 6-OH-DA. Furthermore, the data support the view that the noradrenaline and PNMT containing neurons constitute separate neuron systems.