Effects of Neonatal Hypoxia and Antidepressant Fluoxetine on Cognitive and Stress-Hormonal Functions in Adult Rats

Spatial learning and the functionality of spatial memory, as well as the stressful reactivity of the hypothalamus–pituitary–adrenocortical axis (the HPA axis) were investigated in adult male and female rats, subjected to moderate acute hypoxia on the 2nd day of life, and then to chronic administration of the serotonin reuptake inhibitor fluoxetine. When testing spatial learning in adult rats subjected to neonatal hypoxia, an increase in the latent period of reaching the platform in the Morris water maze in the first trial on the first of five days of training was found. The results of memory analysis in the “Novel Object Recognition” test and in the Morris water maze testify that hypoxia did not cause memory deficiency in adult animals. Moreover, hypoxia improved the memory indices on the first day in males and on the fourth day in females after removing the platform from the tank compared to the corresponding control values. The content of corticosterone in blood plasma of males in response to memory testing did not differ between control and experimental groups and was characterized by higher rates than in females of corresponding groups. Hypoxia increased the HPA axis reactivity in females, which was combined with longer memory storage. Fluoxetine normalized the indicator of spatial learning, did not cause changes in control animals and did not change the identified improvement of memory in hypoxic rats without administration of this drug. The data obtained expand the idea of the long-term effect of normobaric moderate neonatal hypoxia on spatial memory and the HPA axis reactivity depending on sex and emphasize the absence of the harmful effect of fluoxetine on spatial memory in both control rats and in rats subjected to hypoxia.