Noradrenaline neuron plasticity in developing rat brain: effects of neonatal 6-hydroxydopamine demonstrated by...

The present study was conducted to assess the morphological changes produced by neonatal administration of 6-hydroxydopamine (6-OHDA) in the noradrenergic innervation of the developing and adult rat brain. As demonstrated by dopamine-beta-hydroxylase (DBH) immunohistochemistry, the major alterations are the following. First, neocortical and hippocampal noradrenergic innervation is permanently eliminated by the treatment, with lesser effects on other telencephalic structures. These changes appear by postnatal day 5 and are permanent in nature. In adult treated animals, most thalamic nuclei are hyperinnervated by DBH-immunoreactive axons as are the cerebellum and a number of brainstem nuclei. The hyperinnervation of these structures occurs after postnatal day 20, and is extremely specific, with the pattern of organization and distribution of noradrenergic axons in treated animals identical to that of controls. In contrast, the noradrenergic innervation of the hypothalamus is relatively unaffected by 6-OHDA treatment. The principal exception is the development of an anomalous plexus of DBH immunoreactive axons in the lateral hypothalamus. The timing and organization of the changes produced by neonatal 6-OHDA administration are consistent with the hypothesis that noradrenergic neurons, and particularly those of the locus coeruleus, are programmed to produce a defined amount of axon and terminal field, with any developmental loss resulting in a 'pruning effect' such that the total terminal field appears conserved. Given the specificity of the hyperinnervation, inductive influences from the target nuclei probably play a major role in determining the pattern of the noradrenergic innervation.