Noradrenaline Nerve Terminals in the Cerebral Cortex: Effects on Noradrenaline Uptake and Storage Following Axonal Lesion With 6‐hydroxydopamine

The ascending noradrenaline‐containing neuronal system from the locus coeruleus to the cerebral cortex was unilaterally lesioned by an intracerebral injection of 8 μg 6‐hydroxydopamine in the dorsomedial reticular formation in the caudal mesencephalon. The 6‐hydroxydopamine caused injury to axons of the dorsal catecholamine bundle associated with its specific neurotoxic action, while very limited unspecific tissue necrosis was observed. Following this treatment the endogenous noradrenaline in the ipsilateral cerebral cortex (neocortex) increased acutely (up to 2 days), as observed both with noradrenaline assay and fluorescence histochemistry. The noradrenaline concentration then gradually decreased to 15 per cent of the contralateral side 15 days after the lesion. At this time interval and up to at least 90 days no fluorescent catecholamine nerve terminals could be detected. The acute noradrenaline increase could be blocked partially by tyrosine hydroxylase inhibition produced by α‐methyl‐p‐tyrosine. The disappearance of endogenous noradrenaline following tyrosine hydroxylase inhibition was also reduced after the 6‐hydroxydopamine lesion. Studies on the in vitro uptake of [3H]noradrenaline (0.1 μM for 5 min) in slices from the neocortex after the 6‐hydroxydopamine lesion showed a gradual decline in uptake reaching maximal reduction (35‐40 per cent of the contralateral side) after 15 days. No recovery of [3H]noradrenaline uptake was seen up to 90 days after the lesion. The formation of [3H]noradrenaline from [3H]dopamine in vitro was reduced to 15 per cent of the contralateral side after a chronic lesion. The present results indicate that the disappearance of noradrenaline uptake‐storage mechanisms in the neocortex is due to an anterograde degeneration of axons and nerve terminals of the dorsal catecholamine bundle. The data on endogenous noradrenaline and noradrenaline synthesis suggest that approx. 15 per cent of the noradrenaline nerve terminals in the neocortex remain intact following the lesion, while the [3H]noradrenaline uptake data reflect uptake in other tissue structures in addition to noradrenaline nerve terminals, e.g. dopamine nerve terminals, pericytes and/or glial cells.