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

Abstract

BACKGROUND: In recent years, research has focused on understanding the role of orexins and their receptors in regulating the emotions, motivations and brain reinforcing systems. Orexin plays a crucial role in the extrahypothalamic system of corticotropin-releasing hormone, making it a potential target for developing pharmacological agents to treat phobic spectrum disorders.

AIM: The study aims to analyze the effect of the new OX1R antagonist, antorex, on emotional manifestations of anxiety in rats.

MATERIALS AND METHODS: The experiments involved 38 Wistar male rats. Antorex, at a concentration of 1 µg/µl (or water as control), was intranasally administered in a volume of 20 µl (10 µl in each nostril). A battery of behavioral tests was employed, including the 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, as evidenced by the increase in the time spent in the light arm compared to the control group. The marble test revealed a decrease in the number of buried balloons after antorex administration, indicating a reduction in obsessive-compulsive state of anxiety. The anxiety-phobic state assessment test demonstrated a decrease in the avoidance reaction to the hand’s action. In the “open field” test, a decrease in motor activity was observed.

CONCLUSIONS: The OX1R antagonist antorex demonstrated an anxiolytic and sedative effect, reducing compulsive behavior without affecting the communicative activity. These findings support the potential use of drugs that modulate orexin regulation as a novel approach in the treatment of phobic spectrum disorders.

Keywords

orexin / OX1R antagonist / antorex / anxiety / compulsiveness

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