Developmental characteristics of central monoamine neurons and their reciprocal relations

Abstract

The effects of neonatal administration of the monoamine neurotoxins 6-hydroxydopamine and 5,7-dihydroxytryptamine on the postnatal development of monoamine nerve terminals in various regions of rat brain have been investigated. 6-Hydroxydopamine is known to induce a selective degeneration of catecholamine neurons, and 5,7-dihydroxytryptamine has a preferential action on 5-hydroxytryptamine neurons. Monoamine nerve density was monitored by measuring the in vitro uptake of [ 3H] monoamines in brain tissue homogenates, combined with pharmacological analysis and fluorescence histochemistry. It was consistently observed that the relative reductions of [ 3H]monoamine uptake in the cerebral cortex and neostriatum were quantitatively the same 6 to 7 days after the neurotoxin treatment compared with the situation when the uptake analysis was performed on tissues from adult rats. These results indicate that the neurotoxin in these regions produces damage and permanent denervation of a certain number of monoamine nerve terminals, whereas spared nerves undergo an apparent normal development. It was confirmed that the marked and permanent reduction in [ 3H]noradrenaline uptake in the cerebral cortex induced by systemic 6-hydroxydopamine treatment at birth was associated with a considerable increase in [ 3H]noradrenaline uptake in the pons-medulla. This treatment had no effects on uptake in 5-hydroxytryptamine and dopamine nerve terminals. Analogous changes with respect to 5-[ 3H]hydroxytryptamine uptake was observed after neonatal 5,7-dihydroxytryptamine treatment. These plastic changes are most likely due to a “pruning effect” induced by the neurotoxins. The activity of phenylethanolamine N-methyltransferase, a marker of adrenaline neurons, developed normally, independent of the changes in noradrenaline neurons induced by 6-hydroxydopamine. The present results favor the view that the postnatal development of nonoamine nerve terminals is strictly ordered. Furthermore, the neurons exhibit an apparently high degree of intrinsic growth regulation, especially with respect to quantity of nerve terminal arborization. There was no evidence for any interaction between growing monoamine neurons.