Analysis of melanocyte-stimulating hormone role in regulation of emotional and exploratory behavior in rats

Background: Animals’ emotions and exploratory behavior are significant markers of its cognitive and neurobiological health.

Aim: To investigate the effect of a melanocortin-stimulating hormone antagonist on the emotional and exploratory behavior of male rats.

Methods: A series of experiments included a group of 20 male Wistar rats, with a baseline weight of 200–220 grams. A behavioral test battery was used, including Open-Field test, Elevated Plus Maze test, Resident-Intruder test, and Porsolt Forced Swim test. The sample size was fixed at 10 animals per group. ML-00253764, a melanocortin receptor 4/α-melanocyte-stimulating hormone receptor antagonist, diluted in distilled water at 1 mg/mL was administered intranasally at 20 µg (10 µ/mL in each nostril) 15 minutes prior to the behavior testing. Additionally, 0.9% sodium chloride solution was administered in a similar dose to serve as a control.

Results: Intranasal administration of the MC4R antagonist ML-00253764 has been demonstrated to reduce anxiety, enhance research activity, and produce antidepressant effects. In the Open-Field and Elevated Plus Maze tests, an increase in the number of locomotor responses, exploratory activities, and time in open arms was observed, suggesting the activation of exploratory behavior and the anxiolytic effect of the compound. In the Porsolt Forced Swim test, a decrease in immobilization time was documented, which is indicative of the antidepressant effect The Resident-Intruder test demonstrated a decrease in aggressive and defensive behaviors, thereby indicating a normalized social behavior.

Conclusion: The study findings highlight the significance of the melanocortin system in the regulation of emotional and cognitive functions, thereby offering novel insights into the potential therapeutic benefits of MC4R antagonists for the treatment of anxiety and depression.