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Updated: Mar 29, 2026

Restraint to Induce Stress in Mice and Rats
Published on: December 6, 2024
Expression of Melanocortin-4 Receptor mRNA in Male Rat Hypothalamus During Chronic Stress
Maryam Karami Kheirabad1, Bahia Namavar Jahromi2, Amin Tamadon3
1Department of Basic Sciences, Azad University, Gachsaran Branch, Gachsaran, Iran.
Abstract:
The effects of chronic stress and glucocorticoids receptor antagonist (RU486) on expression of melanocortin 4 receptor (MC4R) mRNA in arcuate nucleus (ARC) of male rats were evaluated. In this study, adult male Sprague Dawley rats were placed into four groups (n=6/group); stress, RU486, stress/RU486, and control groups. In stress group, the rats were restrained, 1 h/day, for 12 days. In RU486 group, the rats were injected RU486 for 12 days. In stress/RU486 group, the rats were injected RU486 1 h before the stress process for 12 days. Relative expression of MC4R mRNA was determined using real-time PCR. Relative expression of MC4R mRNA in the stress group was higher than that of the control rats (P<0.05). Relative expressions of MC4R mRNA were not different between the stress, RU486 and stress/RU486 groups (P>0.05). Chronic restraint stress causes increase in mRNA expression of MC4R in ARC and blockade of glucocorticoid receptors has no effect on this up-regulation.
Insights
Chronic stress increases melanocortin 4 receptor (MC4R) mRNA in the brain's arcuate nucleus (ARC) in male rats. Blocking glucocorticoid receptors with RU486 did not alter this stress-induced up-regulation of MC4R.
Area of Science:
- Neuroendocrinology
- Stress Physiology
- Molecular Biology
Background:
- The melanocortin 4 receptor (MC4R) plays a crucial role in regulating energy balance and appetite.
- Chronic stress and glucocorticoids are known to influence neuroendocrine pathways involved in metabolism.
- Understanding the interplay between stress, glucocorticoid signaling, and MC4R expression is vital for metabolic research.
Purpose of the Study:
- To investigate the impact of chronic stress on MC4R mRNA expression in the arcuate nucleus (ARC) of male rats.
- To determine if glucocorticoid receptor blockade using RU486 affects stress-induced changes in MC4R mRNA levels.
Main Methods:
- Adult male Sprague Dawley rats were subjected to chronic restraint stress, RU486 administration, or a combination of both for 12 days.
- A control group received no treatment.
- Relative MC4R mRNA expression in the ARC was quantified using real-time PCR.
Main Results:
- Chronic restraint stress significantly increased MC4R mRNA expression in the ARC compared to controls (P<0.05).
- No significant differences in MC4R mRNA expression were observed between the stress, RU486, and stress/RU486 groups.
- Glucocorticoid receptor blockade with RU486 did not attenuate the stress-induced increase in MC4R mRNA.
Conclusions:
- Chronic restraint stress up-regulates MC4R mRNA expression in the arcuate nucleus of male rats.
- Blockade of glucocorticoid receptors does not influence the stress-mediated increase in MC4R mRNA expression in this model.
- These findings suggest that the effects of chronic stress on MC4R expression in the ARC may be mediated through glucocorticoid-independent pathways.

