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This study was designed to test the authors' hypothesis that dopamine passes from dopamine-synthesizing cells in the brain to the systemic circulation prior to the formation of the blood-brain barrier during ontogenesis. High-performance liquid chromatography studies demonstrated that peripheral blood dopamine levels before formation of the blood-brain barrier-in rat fetuses and neonates-are significantly higher than after formation of the barrier in adult rats, providing indirect evidence in support of the hypothesis. Furthermore, formation of the blood-brain barrier is accompanied by a significant increase in dopamine levels in the rat brain. Direct evidence for the hypothesis was obtained in the form of a sharp decrease in blood dopamine levels in fetuses after lesioning of dopamine-synthesizing neurons in the brain by encephalectomy.

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1. The present study aimed to develop a pharmacological model of catecholamine (CA) depletion in the hypothalamus during the period of its morphofunctional development, i.e. in fetal and neonatal rats of both sexes. 2. In the first series of experiments, pregnant females and, hence, fetuses were systemically treated daily from the embryonic day (E) 13 to E20 with the inhibitor of the CA synthesis alpha-methyl-m-tyrosine. The CA concentrations were subsequently measured in the fetal hypothalamus at E21 by high performance liquid chromatography with electrochemical detection (HPLC-ED). In the second series of experiments, neonatal rats were injected with neurotoxin, 6-hydroxydopamine and/or alpha-methyl-m-tyrosine daily from the 2nd postnatal day (P2) to P10. 3. The HPLC-ED assay of hypothalamic catecholamines (CA's) at E21 and P11 showed that both in fetuses and neonates, alpha-methyl-m-tyrosine caused more than 50% depletion of hypothalamic noradrenaline and adrenaline, while the dopamine (DA) level remained unchanged. The combined treatment of neonatal rats with alpha-methyl-m-tyrosine and 6-hydroxydopamine resulted additionally in a 25% decreased level of DA. 4. The influence of CA deficiency on the developing hypothalamic CA system was further evaluated by measuring [3H]DA uptake by nervous tissue in vitro. 5. The CA deficiency caused a 50% drop of [3H]DA uptake by the hypothalamic tissue in treated fetuses suggesting a stimulating effect of CA's on the early development of the CA system. In pharmacologically treated neonatal rats [3H]DA uptake remained at the control level showing no influence of the CA deficiency on the developing CA system after birth. 6. The usefulness of the proposed pharmacological model for studying of CA influence on differentiating hypothalamic target neurons is discussed.