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Ahmad Siddiqui S, Singh S, Ahmad M K, Arshad M. Altered Serotonin 5HT-1B Receptor Expression Regulate Sex-dependent Difference for Stress and Anxiety. BCN 2025; 16 (1) :81-94
URL: http://bcn.iums.ac.ir/article-1-2476-en.html

Introduction: Stress disorders have multidimensional effects. How we respond to these situations is different, depending on our individual differences and gender. Reports suggest that females are more susceptible to stress disorders compared to males in the same age group. The serotonin receptor system is an important mechanism involved in the regulation of stress and anxiety in males and females. 
Methods: The current study incorporates a rodent model to study the sex-dependent role of serotonin receptors under chronic restrained stress conditions. A chronic restrained stress protocol was used to find the stress difference between male and female Sprague-Dawley (SD) rats. The molecular identification was done using quantitative real-time PCR and immunohistochemistry for serotonin 5HT-1B receptor in rat brains.
Results: Interestingly, the 5HT-1B receptor, one of the most important serotonin receptors, exhibits a sex-dependent difference in stress response in male and female rats. Most importantly, the trio partners (amygdala, hippocampus, and prefrontal cortex) exhibit a region-specific sex dependent difference in 5HT-1B receptor expression, which was correlated with the difference in the level of stress response. This biased serotonin 5HT-1B receptor function might be why females face more stress than males.
Conclusion: Overall, the results exhibit a sex-dependent difference for stress conditions in male and female rats, which was correlated with the spatial expression of the serotonin 5HT-1B receptor in the brain.