Abstract

We tested our hypothesis that dopamine (DA) is secreted from the brain to the blood during the perinatal period of rat ontogeny when rats have no blood-brain barrier. We developed a specific pharmacological model to inhibit DA synthesis in the brain and maintain its constant level on the periphery using α-methyl-p-tyrosine (αMPT), an inhibitor of the key enzyme of DA synthesis tyrosine hydroxylase. On the basis of preliminary systemic administration of αMPT (200, 100, 80, and 50 μg), we selected a dose of the inhibitor of 50 μg, which excluded its effects on DA metabolism in peripheral organs. In subsequent experiments, αMPT was stereotaxically administered into the lateral brain ventricles of three-day-old rats at the selected dose. After this, we measured the concentration of catecholamines and metabolites using high performance liquid chromatography with electrochemical detection in the brain, Zuckerkandl’s organ, kidneys, adrenals, and plasma. We found that in 4 h after administration of the inhibitor, the DA concentration decreased in the brain by 54% and in the plasma by 74%, whereas in the peripheral organs it remained unchanged. Thus, we directly showed that DA is secreted from the brain in the general blood circulation before the formation of the BBB.

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