Neonatal central catecholaminergic lesions with intracisternal 6- hydroxydopamine: effects on development of presynaptic and postsynaptic components of peripheral sympathetic pathways and on the ornithine decarboxylase/polyamine system in heart, lung and kidney

TA Slotkin, FJ Seidler, K Haim, AM Cameron, L Antolick and C Lau

Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.

Peripheral sympathetic neurons are thought to provide trophic regulatory signals for development of adrenergic target tissues. In the current study, we destroyed central catecholaminergic pathways in the neonatal rat by intracisternal administration of 6-hydroxydopamine, which compromises sympathetic tone without ablating peripheral nerve terminals. Measurements of norepinephrine levels and turnover confirmed the effectiveness of the treatment in projections to heart, lung and kidney. The impairment of sympathetic tone was associated with a deficit in cardiac beta adrenergic receptor binding capabilities; in contrast, binding sites in the lung were unaffected and renal receptors were up-regulated. Similarly, intracisternal administration of 6- hydroxydopamine produced tissue-selective alterations in ornithine decarboxylase activity and levels of the polyamines. These results support the view that neural activity exerts an influence on the biochemical development of sympathetic target tissues; however, other trophic factors may derive from the presence of intact nerve terminals themselves, as distinct from activity.

Volume 247, Issue 3, pp. 975-982, 12/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics