Neonatal 6‐hydroxydopamine destroys spinal cord noradrenergic axons from the locus coeruleus, but not those from lateral tegmental cell groups

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Abstract
Subcutaneous injection of 6‐hydroxydopamine (6‐OHDA) in neonatal rats results in sprouting of collateral axons in locus coeruleus (LC) and lateral tegmental noradrenergic neurons. It has been suggested that this sprouting represents maintenance of neuronal membrane area following “pruning” of axon terminals of long projections to cortex and cord. The chemical or surgical lesions of long axons used to produce “pruning” could also result in the loss of some parent cell bodies. We tested the hypothesis that long axon damage, rather than cell loss, is sufficient to produce collateral sprouting of proximal axons in noradrenergic neurons. With neonatal injections of 6‐OHDA at doses which do not produce a loss of LC neurons, there is an 85% decrease in retrograde LC labeling following horseradish peroxidase or true blue injections into the spinal cord but no significant change in the numbers of retrogradely labeled neurons in other noradrenergic cell groups which also sprout collaterals. There is no change in the number of labeled LC neurons following cerebellar injections. In experiments using the fluorescent dyes diamidino yellow and true blue, the number and distribution of LC neurons labeled from spinal cord and cerebellum injections are similar to those in the horseradish peroxidase experiments. Doubly labeled neurons are found in the caudal two‐thirds of LC in control rats, but as expected, rarely observed in 6‐OHDA‐treated animals. This study demonstrates that (1) cell loss in the LC is not necessary for sprouting following neurotoxin treatment, and (2) the increased number of norepinephrine (NE) terminals in the pons is not due exclusively to a “pruning effect,” since NE cells outside the LC, which are known to contribute to the hyperinnervation, retain their long projections to the spinal cord.