[Development of central and peripheral serotonin-producing systems in rats in ontogenesis].

The work deals with study of development of central and peripheral serotonin-producing systems in rat ontogenesis before and after formation of the blood-brain barrier. By the method of highly efficient liquid chromatography it has been shown that the serotonin level in peripheral blood before formation of the blood-brain barrier (in fetuses and neonatal rats) is sufficiently high for realization of physiological effect on target cells and organs. At the period of formation of the blood-brain barrier the serotonin level in brain sharply rises, whereas the serotonin concentration and amount in plasma and duodenum increase insignificantly. Completion of formation of the blood-brain barrier is accompanied by a significant increase of the serotonin content in duodenum, probably for maintenance of the high serotonin level in blood. To evaluate secretory activity, the mean rate of daily increment of the serotonin in the studied tissues was calculated. In brain, this parameter was maximal at the period of formation of the blood-brain barrier and then sharply fell, whereas in duodenum it rose markedly after completion of the barrier formation. In plasma this parameter decreased statistically significantly at the period of formation of the blood-brain barrier - from the 4th to the 16th postnatal days. This allows thinking that brain before formation of the blood-brain barrier is a most important source of serotonin in peripheral blood.

[Brain is a source of blood serotonin in rats during perinatal development].

The aim of this study was to test our hypothesis that the brain functions as an endocrine organ before the blood-brain barrier is formed. A model of drug-inhibited serotonin synthesis in the brain using a single stereotactic administration of p-chlorophenylalanine, an inhibitor of serotonin synthesis, was developed. The inhibitor dose inducing the maximum effect in the brain and no effect on serotonin synthesis in the periphery was experimentally selected. The concentration of serotonin and its metabolites (5-hydroxytryptophan and 5-hydroxy-indoleacetic acid) was studied by high performance liquid chromatography in the brain, duodenum, and blood (separately in plasma and platelets). The optimal p-chlorophenylalanine dose (200 mg/kg) was shown to induce a sharp decrease in the brain level of serotonin (70%), a moderate decrease in plasma (16%) and platelets (26%), and an insignificant decrease in the duodenum (12%). At the same time, this dose did not decrease the 5-hydroxytryptophan level in the intestine. This suggests that the decrease in the blood level of serotonin was due to the inhibition of its synthesis in the brain, whereas the decrease in the duodenum level of serotonin was due to the compensatory release to blood while its synthetic rate remained unaltered. Thus, the developing brain before the blood-brain barrier formation was shown to secrete serotonin into blood.

[Changes in blood plasma volume in rats during ontogenesis].

The dynamics of blood plasma volume were studied for the first time in rats during ontogenesis. The significance of blood plasma volume is estimated in the transport of physiologically active substances to cells and target organs during development. The blood plasma volume was measured in male and female rats during embryogenesis on day 18 (E18), perinatal development on E21 and day of postnatal development (P3), and postnatal development on P15 and P30. Body mass was determined in the same animals and correlation was estimated between the blood plasma volume and body mass. The plasma volume increased 1.9-fold from E18 to E21, 1.4-fold from E21 to P3, 2.1-fold from P3 to P15, and 3.4-fold from P15 to P30. The body mass increased 5-fold from E18 to E21, 2-fold from E21 to P3, 2.3-fold from P3 to P15, and 3.2-fold from P15 to P30. The ratio of blood plasma to body mass was the highest on E18 (19%) and decreased twice by E21. This index varied from 5.4 to 4.8% during postnatal development. No sex-related differences in these indices were found in rats. The results obtained make it possible to determine the total content of physiologically active substances on the basis of their plasma concentration and, thereby, estimate the efficiency of secretory organs.