Analysis of stressoprotective properties of progesterone on an animal model of post-traumatic stress disorder

Abstract

Relevance. Sex steroid hormones play a fundamental role not only in reproductive biology, regulation of emotions and mood, but also participate in maintaining proper homeostasis of the nervous system, acting as trophic factors and neurotransmitters, while steroids are also synthesized de novo in both central and peripheral nervous system. One of the main neurosteroids is progesterone, and its two important metabolites, namely allopregnanolone (3a,5a-tetrahydroP4) and 3a,5a-tetrahydrodeoxycorticosterone, which due to a combination of genomic and non-genomic effects, have a wide range impact on neural cells. Aim. To analyze the stress-protective properties of progesterone on an animal model of post-traumatic stress disorder. Materials and methods. 40 white mongrel male rats were taken for the purpose of investigation. They were divided into several investigation groups: Con — group of animals receiving intraperitoneal injection of solvent
(n=10); PS — group of animals exposed to vital stress (n=10); PS+P — a group of animals exposed to vital stress and receiving an intraperitoneal oil solution of progesterone in a dose of 8 mg/kg (n=10) for 10 days before a stress exposure; PS+S — a group of animals exposed to vital stress receiving an intraperitoneal solution of sulpiride in a dose of 10 mg/kg (n=10). To simulate a psychotraumatic event, the classical method of imaging a predator was used. To record the changes in emotional-motor patterns among the control and experimental groups a battery of behavioral tests was used, Elevated Cruciform Maze, Open Field, and Porsolt test. Results. Changes in behavioral patterns were observed after administration of progesterone to animals that had been exposed to a psychotraumatic event. The impact on the “emotionality” zone was characterized by a reliable increase in the number of sniffing (p?0.05), and a significant increase of locomotor activity was also observed (p?0.05). In the Elevated Cruciform Maze test, the anxiolytic effect of progesterone was demonstrated, which consisted of a decrease in the time experimental animals spent in the closed arm of the installation and, accordingly, of an increase in the time animals stay in the open arm, which may indicate a decrease in the level of anxiety. Porsolt test demonstrates that the antidepressant effect of progesterone is to normalize the timing of behavioral patterns in animals exposed to a stressor. Conclusion. As a whole, the results of our study demonstrate that intraperitoneal administration of an oily progesterone solution at a dose of 8 mg/kg has pronounced anxiolytic and antidepressant effects according to the results of a series of behavioral tests in the predator presentation stress model.