BACKGROUND: Currently, no study has investigated on the role of ghrelin in the reinforcing system and emotional behavior. Previously, we examined the properties of GHSR1A antagonist [D-Lys3]-GHRP-6 to reduce negative emotional states caused by stress. AIM: To study the involvement of a new peptide antagonist of the GHSR1A receptor agrelax in the control of emotionalexploratory behavior and anxiety in rats. MATERIALS AND METHODS: Experiments were performed on 42 male Wistar rats. The behavior of rats was observed; agrelax 1 g/mL (or water) with a volume of 20 L (10 l in each nostril) was administered intranasally. A battery of behavioral tests was used: an elevated plus maze, an open field, a marble test, an intruderresident test, and an anxiety-phobic state assessment (FS). RESULTS: In the elevated plus maze test, the time spent in the light arm and the number of hangings from the open arm increased in the test animals compared with animals that did not receive the drug (p 0.05). After the administration of agrelax, the number of balloons buried and the number of elevations supported by the wall of the chamber in the marble test decreased compared with that in animals that did not receive the drug (p 0.05). In the open field, agrelax-infected rats showed a decrease in the number of sniffs (p 0.01). In the FS test after the agrelax administration, the time of descent from the platform decreased compared with the control (p 0.05). In the intruderresident test, individual behavior (p 0.01) and protective behavior (p 0.05) decreased after agrelax administration. CONCLUSION: A new peptide antagonist of the GHSR1A receptor agrelax is involved in the control of emotionalexploratory behavior in rats. Agrelax reduced anxiety levels and exploratory activity. The results provide grounds for the development of new approaches to the treatment of phobic spectrum disorders using drugs that modulate ghrelin regulation.
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.
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