Inhibition of catecholamine synthesis during ontogenic development

Abstract

The decrease with time of dopamine (DA) and noradrenaline (NA) in whole brain was analyzed in rats at 1, 4, 10, 14 and 21 days postnatal age following inhibition of tyrosine hydroxylase with H 44/68 (α-methyl- p-tyrosine-methylester) or of dopamine-β-oxidase with FLA-63 (bis[4-methyl-1-homopiperazinylthiocarbonyl]-disulfide). Over the time studied (up to 4 h after injection), the level of DA remained relatively constant at 1 day of age following treatment with H 44/68. At 4 and 10 days of age, there was a marked decrease in DA up to 2 h with no further change at 4 h, thereby producing a marked biphasic disappearance curve. At 14 and 21 days, the DA levels decreased continuously with time, but still with a slight biphasic tendency. NA decreased significantly from 1 day of age following treatment with H 44/68. After FLA-63, NA levels decreased at a much more rapid rate than after H 44/68 and DA accumulated to a slight degree. In a separate study on animals at 4 and 14 days of age, the decrease in DA and NA content was determined in brain regions 2 h after injection of H 44/68. At 4 days, a statistically significant decrease in DA content was noted only in the striatum, whereas at 14 days of age DA decreased significantly in all regions analyzed. NA decreased significantly at both 4 and 14 days in all regions except the striatum. The results indicate that NA-containing neurons become functional ( i.e. impulse conducting) at an earlier age than DA-containing neurons and also that DA-containing neurons present in the brain become functional at different postnatal ages.