Emotiogenic effects of аntorex, a novel OX1R antagonist, on emotional manifestations of anxiety and compulsiveness in rats

Abstract

Background. In recent years, the role of orexins and their receptors in the regulation of the emotions, motivations and brain reinforcing systems has been studied. Orexin is an important regulator of the extrahypothalamic system of corticotropin-releasing hormone. This provides grounds for the search for new pharmacological agents for the treatment of phobic spectrum disorders among drugs that modulate orexin regulation. Aim: To analyze the effect of the new OX1R antagonist Antorex on the emotional manifestations of anxiety in rats. Methods. Experiments were performed on 38 Wistar male rats. Behavior was tested in rats; Antorex 1 g/l (or water) with a volume of 20 l (10 l in each nostril) was intranasally administered. To achieve this goal, a battery of behavioral tests was used: elevated plus maze, open field, marble test, intruder-resident test and anxiety-phobic state assessment. Results. In the elevated plus maze test, Antorex showed moderate anxiolytic activity, increasing the time spent in the light arm compared to control animals. In a marble test, after Antorex administration, a decrease in the number of buried balloons was observed, as a reflection of a decrease in the obsessive-compulsive state of anxiety. In the anxiety-phobic state assessment test, a decrease in the avoidance reaction to the action of the hand was registered. In the "open field" test, a decrease in motor activity was observed. Conclusion. The OX1R antagonist Antorex has an anxiolytic and sedative effect reducing compulsive behavior without affecting the communicative activity. The data obtained provide grounds for the development of new approaches to the treatment of phobic spectrum disorders using drugs that modulate orexin regulation.