DOPAMINE ACCUMULATION IN THE MOUSE BRAIN UNDER HYPOXIA

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Effects of hypoxia on brain catecholamines were investigated in mice using high-performance liquid chromatography combined with electrochemical detection. When mice were exposed to hypoxic gas mixtures containing 6 or 7% oxygen, dopamine (DA) accumulated in the brain, regardless of the body temperature of the mice. Hypoxia-induced DA accumulation was greater in the norepinephrine (NE) rich areas (cerebellum, cerebral cortex and pons+medulla oblongata) than in the DA rich area (striatum). The DA depletion induced by inhibition of tyrosine hydroxylase with α-methyl-p-tyrosine was markedly inhibited by hypoxia. The brain homovanillic acid (HVA) accumulation induced by inhibiting active transport of organic acid with probenecid was also significantly inhibited by hypoxia while brain HVA levels were unchanged. The brain 3, 4-dihydroxyphenylacetic acid (DOPAC) level and probenecid-induced DOPAC accumulation were not significantly affected by hypoxia. These findings indicate that hypoxia inhibits DA-β-hydroxylase in the NE rich areas and results in an accumulation of DA, as the NE precursor, while hypoxia-induced DA accumulation in the DA rich area may be due to an inhibition of monoamine oxidase and/or of DA release.
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