Metabolism of Catecholamines in the Developing Spinal Cord of the Rat

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Abstract
The metabolism of 3,4-dihydroxyphenylethylamine (DA, dopamine) and norepinephrine (NE) both normally, and after the administration of levo-3,4-dihydroxyphenylalanine (l-DOPA), has been studied in several regions of the developing spinal cord of the rat from fetal day (FD) 16 to the young adult stage. During late fetal (from FD 16) and most of neonatal life [to neonatal day (ND) 20], dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were either just detectable or present in very low concentration in all regions in the untreated developing rat. However, the developing spinal cord possesses an enormous capacity to metabolize the large amounts of DA synthesized from injected l-DOPA. At the end of 1 h after 100 mg/kg i.p. of l-DOPA, DOPAC and HVA are 54 ± 14 (n = 5) and 16 ± 5 (n = 5) nmol/g, respectively, in the thoracic zona intermedia in the 12h-old (ND 0.5) rat. This metabolic capability is already highly developed as early as FD 16, peaks during the first half of neonatal life (ND 4 for DOPAC, and ND 15 for HVA), and is considerably reduced toward the end of neonatal life (approximately ND 28) and in the young adult. Control experiments suggest that a substantial part of this synthesis (from l-DOPA) and metabolism of DA occurs in elements other than the descending monoaminergic nerve fibers. By comparison, the synthesis and metabolism of NE develop more slowly, peak in the latter half of neonatal life, and then decline to the level found in the young adult. In the ventral horn of the lumbar region, however, the capacity to metabolize NE develops more rapidly than in the dorsal horn and zona intermedia. The results suggest that the activities of several enzymes involved in the synthesis (aromatic amino acid decarboxylase) and inactivation of catecholamines (monoamine oxidase and catechol-O-methyltransferase) are already highly developed by FD 16, and achieve their highest activities in the spinal cord during early neonatal life.