6-HYDROXYDOPAMINE DURING DEVELOPMENT - RELATION BETWEEN OPPOSITE REGIONAL CHANGES IN BRAIN NORADRENALINE

The perinatal injection of the neurotoxic compounds 6-hydroxydopamine and 6-hydroxydopa, persistently alters the ontogenesis of central noradrenergic neurons in rats, i.e. there is a long-lasting elevation of noradrenaline (NA) in the brain stem and the cerebellum and a reduction in the cortex and spinal cord NA. The latter has been interpreted as due to the destruction of NA-containing terminals while the increase of NA in the brain stem seems to result from a neuronal outgrowth thought to be the response to forebrain denervation. To study the importance of this process for the increase of brain stem NA, various doses of 6-hydroxydopamine were given intraventricularly at birth. Small amounts of the compound (12.5-50 μg) produced the expected effects but 75 μg, while similarly depleting cortical and spinal NA, failed to increase NA levels in the brain stem and the cerebellum. This dissociation could be due to the fact that the high dose of 6-hydroxydopamine altered the noradrenergic neurons to such an extent as to prevent their sprouting when stimulated by the denervation. However, the systematic injection of 6-hydroxydopa given at 3 days of age, increased brain stem NA to a comparable extent in non-treated rats and in those that received 75 μg of 6-hydroxydopamine at birth. These results suggest that forebrain denervation is not the sole stimulus responsible for triggering the processes leading to the increase of NA in the brain stem. © 1979.