6-Hydroxydopamine treatment of neonatal rats. I. Effects on the development of the spinal cord noradrenergic system

The spinal cord contains noradrenergic (NA) pathways which descend from cell bodies in the medulla oblongata and pons to terminate at all levels in the spinal gray matter. The present studies sought to determine the patterns of postnatal development of pre- and postsynaptic elements of NA transmission in the spinal cord. Significant presynaptic development is evident at birth as reflected by substantial high-affinity uptake of norepinephrine (NE) into synaptosomes (0.65-0.90 pmol/mg protein). There is a subsequent increase in uptake on postnatal day (PND) 5, followed by a decrease in 5-10 days to essentially adult levels, starting on PND 20 (0.30-0.35 pmol/mg protein). This decrease in NE uptake occurs coincident with increases in the density of postsynaptic α₁ and β adrenergic receptors and also NE-stimulated accumulation of 3′,5′-cyclic adenosine monophosphate (cAMP). Peaks in the development of α₁ receptors (PND 10) and β receptors (PND 20) and NE-stimulated cAMP accumulation (PND 15) were also followed by decreases to adult levels. The neurotoxin 6-hydroxydopamine (6-OHDA) was administered at birth to determine the effects of denervation on the development of the spinal NA systems. At each day following 6-OHDA, synaptosomal uptake of [³H]NE was reduced by two-thirds compared with control values. α₁ and β adrenergic receptor binding are uniformly increased along with a parallel increase in NE-stimulated accumulation of cAMP. While uniformly increased over control, the pattern of postnatal increases and decreases in receptors and cAMP accumulation is maintained. These results suggest that developmental signals for the expression of α₁ and β receptors and adenylate cyclase activity in the postsynaptic receptor systems are maintained despite the loss of presynaptic input from descending NA pathways.