Effect of Hypoxia on Monoamine Synthesis in Brains of Developing Rats

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Abstract
Tyrosine and tryptophan hydroxylase activity was studied in vivo in the postnatal rat brain by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) respectively after inhibition of Z-aromatic amino acid decarboxylase with NSD 1015. 1-, 4-, 14- and 28-day-old rats were exposed to a 12% oxygen environment for a period of 30 min, 2 and 6 h. After 30 min in the 12% oxygen environment the tryptophan hydroxylase activity decreased significantly in all age groups studied, but increased significantly after 6h hypoxia compared to controls in 1- and 4-day-old rats. Tyrosine hydroxylase activity in 1-day-old rats was significantly decreased only after 30 min hypoxia as it returned to normal after 2 and 6 h. In the 4-day-old rats a decrease was noted after 30 min and 6 h. In the 14- and 28-day-old rats a significant reduction of tyrosine hydroxylase activity was found after all the time intervals studied. It is concluded that the oxygen dependent, first, rate-limiting step in the synthesis of the neurotransmitters dopamine, noradrenaline and 5-hydroxytryptamine seems to be less vulnerable in the brains of early postnatal rats. Decreases and increases of the levels of tryptophan correlated well to the found changes in 5-HTP levels. This correlation did not seem to be present in the case of tyrosine and DOPA accumulation. It is thus suggested that the observed changes in tryptophan hydroxylation may in part depend on the changes in tryptophan availability. This did not seem to be the case concerning tyrosine hydroxylation and tyrosine availability.