Effect of SB-408124, an orexin A OX1R receptor antagonist, on the compulsive behavior and the level of anxiety after the vital stress in rats

Abstract. The effect of the orexin A OX1R receptor antagonist SB-408124 of on the compulsive behavior and the anxiety in rats after the presentation of vital stress in a number of behavioral tests: marble test, elevated plus maze, in the open field and in the test “resident intruder”. In the buring marble test, the behavioral components of the obsession  (obsessive  and obtrusive thoughts) and compulsions (obtrusive behavior), aimed to reduce anxiety, were modeled. Mental trauma was caused by a stressful effect, the essence of which was the experience of the animals of the circumstances of the death of a partner from the actions of a predator. A group of rats were placed once in the terrarium to a tiger python. After the action of vital mental stress in rats, two connected behavioral phenomena were observed: a high level of anxiety and an increase in the number of buried balls. This was accompanied by a decrease in communicability. Intranasal administration (for 7 days) of orexin A antagonist OX1R receptor SB-408124 after presentation of the vital stress reduced the level of anxiety, and also normalized the communicative activity of animals and the number of buried balls, i.e. compulsive behavior. Thus, the orexin system of the brain is an important component of psychotraumatic mechanism. OX1R antagonists of orexin A receptors can potentially be considered as correctors of obsessive-compulsive disorders on the background of posttraumatic stress disorder (PTSD). Use of intranasal administration of OX1R antagonists of orexin A receptors in the clinic will allow the use of small doses of substances and thereby reduce their possible toxic effects.