Developmental plasticity of central noradrenaline neurons after neonatal damage?changes in transmitter functions

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Abstract
The effects of neonatal 6‐hydroxydopamine (6‐OH‐DA) treatment (systemic administration) on norasrenaline (NA) metabolism, trun over, and receptor charasteristics have been investigated in rat brain in the adult atage. This treatment is known to preferentially affect the locus coeruleus (LC) NA system leading to a marked NA denervation in the cerebral cortex and a hyperinnervation of NA nerve terminals in the pons and medulla oblongata without influencing the LC perikarya. The main NA metabolite, 3‐methoxy‐4‐hydroxyphenylglycol (MOPEG) was reduced by about 70% in the cerebral cortex after 6‐OH‐DA‐treatment at birth while the endogenous NA was almost completely depleted (‐92%). The MOPEG levels were not significantly changed in the pons medulla after 6‐OH‐DA treatment in contrast to the 60% increase of the endogenous NA concentration. The relative reduction of NA in the cerebral cortex of 6‐OH‐Da treated rats increased in the cerebral cortex is increased after 6‐OH‐DA, while decreased in the pons‐medulla, possibly related to changes in the activation of presynaptic α‐adrenoreceptors in both regions. NA‐induced formation of cAMP in vitro was found to be markedly increased in the cerebral cortex after 6‐OH‐DA, whereas no consistent change was observed in the pons medulla. Measurements of α‐ and β‐receptor binding in vitro using radioligand techniques showed an increase of binding sites (20%–50%) for both receptors in the neocortex after 6‐OH‐DA, whereas no changes were observed in the pons medulla. The 6‐OH‐Da induced changes in NA turnover, cAMP generating systems, and receptor density may all represent compensatory processes following the altered development of the NA neurons induced by 6‐OH‐DA.