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Noradrenaline and dopamine interaction in rat brain during development.

The effects of systemic treatment of newborn rats with the catecholamine neurotoxins 6-hydroxydopamine (6-OH-DA) or N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on the central dopamine (DA) and noradrenaline (NA) neurons were studied using neurochemical techniques. Both neurotoxins cause similar alterations of the postnatal development of the NA neurons with a pronounced NA denervation in the cerebral cortex and a NA hyperinnervation in the pons-medulla. The results did not show any neurotoxic action of neonatal 6-OH-DA or DSP4 treatment on the DA neurons. The tyrosine hydroxylase inhibition model was used to evaluate catecholamine turnover. The data showed a reduced DA turnover both in the cerebral cortex and striatum in young rats (12 days old) after neonatal 6-OH-DA or DSP4 treatment. After 6-OH-DA this effect could be blocked by pretreatment with the NA uptake blocker desipramine, which also prevented the 6-OH-DA induced alteration of the development of NA neurons. No clear-cut effect on DA turnover was seen in the adult stage after neonatal 6-OH-DA or DSP4, although a reduced DA turnover was observed in the cortex after an acute DSP4 treatment in adult rats. The results show that NA nerve terminals originating in the locus coeruleus NA neurons may be involved in regulating the functional activity of the DA nerve terminals both in the cerebral cortex and the striatum. This regulation appears to be facilitatory in nature and is present early in development.