A new ghrelin receptor antagonist agrelax participates in the control of emotional-explorative behavior and anxiety in rats

Abstract

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 emotional–exploratory behavior and anxiety in rats.

MATERIALS AND METHODS: Experiments were performed on 42 male Wistar rats. The behavior of rats was observed; agrelax 1 μg/mL (or water) with a volume of 20 μL (10 μl in each nostril) was administered intranasally. A battery of behavioral tests was used: an elevated plus maze, an open field, a marble test, an intruder–resident 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 “intruder–resident” 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 emotional–exploratory 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.

Keywords

ghrelin / GHSR1A antagonist / agrelax / anxiety

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