Throughout our course this semester, I’ve found that I have a strong interest in sex differences in rodent models of depression and anxiety and the validity of behavioral tests. In each paper we’ve read and discussed, I’ve paid particular attention to whether or not both male and female animals are used and how closely the behaviors they test seem to represent anxiety and/or depression. While some neurological and hormonal/chemical methods for assessing anxiety in these animals have been identified that parallel those in humans, I am especially interested in how these changes can manifest as behaviors that we can align with our own. For these reasons, I have chosen to write a review of behavioral sex differences in rodent models of anxiety for my final paper. I plan to use existing literature to investigate the efficacy of different stress paradigms in inducing anxiety in male vs. female rodents, the differences in behavioral responses of males and females to existing tests of anxiety, and what sex-specific stress paradigms and behavioral tests have been created.
In the literature I have reviewed thus far, I’ve found that many of the same anxiety- and depression-inducing stress paradigms we’ve seen during class have been used for both males and females. In particular, chronic unpredictable stress and chronic mild stress, and a similar paradigm—variable stress—have been used in an effort to cause anxiety-like behaviors in rodents (Dalla et al., 2005, Johnson et al., 2020, Palumbo et al., 2020). In each of these studies, both males and females demonstrated anxiety-like behaviors, though there were some sex differences between behavioral outputs. Anxiety-like behaviors were measured in both sexes by common tests such as the open field test, novelty suppressed feeding, the elevated plus maze, and social interaction tests, as well as tests that are less familiar to me including the splash test (which measures grooming behaviors after splashing a mouse with a sucrose solution) and a novel cage observation of various behaviors. Sex differences in behavior cannot yet be generalized or compared across studies given the limited number of research reviewed at the time being, though there seem to be some conflicting reports about whether stress paradigms increase or decrease locomotor activity in female rodents (Palumbo et al., 2020, Dalla et al., 2005). Additionally, there seems to be a level of consensus about higher susceptibility to anxiety among females compared to males. I have also found that some sex-specific paradigms for inducing anxiety have been used, such as the early social isolation procedure used by Kumari et al. (2016) to induce anxiety in females. I look forward to learning about additional sex-specific paradigms and additional ways in which sex mediates behavioral responses to anxiety.
Sources
An, X., Zou, J., Wu, R., Yang, Y., Tai, F., Zeng, S., . . . Broders, H. (2011). Strain and sex differences in anxiety-like and social behaviors in C57BL/6J and BALB/cJ mice. Experimental Animals, 60(2), 111-123.
Dalla, C., Antoniou, K., Drossopoulou, G., Xagoraris, M., Kokras, N., Sfikakis, A., & Papadopoulou-Daifoti, Z. (2005). Chronic mild stress impact: Are females more vulnerable? Neuroscience, 135(3), 703-714. Doi: 10.1016/j.neuroscience.2005.06.068
Johnson, A., Rainville, J., Rivero-Ballon, G., Dhimitri, K., & Hodes, G. (2020). Testing the Limits of Sex Differences Using Variable Stress. Neuroscience, Neuroscience, 07 January 2020.
Kumari, A., Singh, P., Baghel, M., & Thakur, M. (2016). Social isolation mediated anxiety like behavior is associated with enhanced expression and regulation of BDNF in the female mouse brain. Physiology & Behavior, 158, 34-42.
Palumbo, M. C., Dominguez, S., & Dong, H. (2020). Sex differences in hypothalamic–pituitary–adrenal axis regulation after chronic unpredictable stress. Brain and Behavior. doi: 10.1002/brb3.1586
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