ИСТИНА

It is well known that serotonin (5-HT) plays a key role in early brain development, and manipulation of 5-HT levels during this period can have lasting neurobiological and behavioral consequences. Selective serotonin reuptake inhibitors (SSRI) are the most common pharmacological treatment for depression during pregnancy. The antidepressants of the SSRI group pass through the placental barrier and can act directly on the fetal serotonergic system [1]. Disturbance of the serotonergic system during pregnancy affects emotional state and cognitive function of offspring [2]. However, the consequences of perinatal SSRI exposure are not completely known. Heptapeptide Semax is an analog of the ACTH(4-10) fragment. Now Semax is used in clinic to correct nervous system diseases, such as vascular brain damage, stroke, traumatic brain injury. It has a multifactorial neuroprotective effect, combining the properties of a neuroprotector, neurometabolic, antioxidant and nootropic agent [3]. The aim of present work was to study the possibility of correction of the negative effects of perinatal SSRI fluvoxamine (FA) administration by Semax treatment. Methods: The work was carried out in male and female Wistar rats. FA was injected intraperitoneally at a dose of 10 mg/kg. The drug was administrated in different periods of rat development: (1) - pregnant females were injected with from 3 to 10 days of pregnancy; (2) - pregnant females were injected with FA from 8 to 14 days of pregnancy; (3) – rat pups received FA from 1 to 14 postnatal days. Semax was administrated intranasally at a dose of 0.05 mg/kg for 1st and 2nd postnatal weeks (series 1 and 2) or for 3d and 4th postnatal weeks (series 3). Control animals received vehicle injections at the same administration route and at the same period. Then we have studied anxiety level in “elevated plus maze” test on 31 postnatal day and cognitive abilities in test “food-reinforced maze task” on 40-44 postnatal days. Results: In was shown that FA administration from 3 to 10 days of pregnancy does not affect the emotional state and cognitive function of the offspring. But the drug administration from 8 to 14 days of pregnancy or neonatal FA injections led to significant disruptions of the acquisition of the maze task, as well as to the increase of anxiety level in elevated plus maze. Semax administration improved learning ability and decreased anxiety level in rats received FA in neonatal period, but did not influence on the consequence of FA prenatal administration. Conclusion: Data obtained allow to conclude that FA administration at the earlier embryonic stages of development do not influence on cognitive functions and anxiety. FA administration in the late term of pregnancy can lead to long-term disturbances in the fetal nervous system, because this antidepressant directly affects forming of the fetal serotonergic system. Semax attenuates negative effects of the neonatal, but not prenatal antidepressant administration. Our work was supported by Russian Foundation for Basic Research (grant № 19-04-00209).