Social defeat stress has been shown to induce long-term changes in brain and behavior in both males and females. California Mice Peromyscus californicus Male and female California mice exhibit different behavioral phenotypes in response to social defeat stress. For instance, California mice show increased anxiety-like behavior immediately prior to a third episode of defeat stress Greenberg et al.
Kudryavtseva and colleagues Kudryavtseva et al. Thus, stress-induced reductions in social interaction have strong face and pharmacological validity to social withdrawal behavior observed in stress-induced psychiatric disorders. For example, after a short physical confrontation, a focal mouse is separated from the resident by a clear, perforated divider placed in a shared homecage. A mouse Warren et al. Focal animals are randomly assigned to stress or control conditions, which controls for intrinsic differences in aggressive behavior and competitive ability. Stressed females, but not stressed males, show decreased social interaction after exposure to 3 consecutive days of social defeat consisting of 7 minutes or 7 attacks Trainor et al. In most cases, the focal animal is an intruder in an unfamiliar cage and is unlikely to be aggressive toward the resident. Sensory contact is an important component of the most widely used protocols for male C57 mice Golden et al. However, most of the basic research examining the neurobiological mechanisms of these disorders has been conducted with male rodents. Using these new female models, recent studies have examined how social defeat stress affects males and females differently at the behavioral, circuit, and molecular levels. Interestingly, there is a significant variability in sensitivity to social defeat across species. However, the development of social defeat stress protocols in female rats, hamsters, and California mice has created new opportunities to consider sex differences in how stress impacts the brain. Specific protocols vary across species and laboratories, with a common thread consisting of aggressive physical contact with a more aggressive individual. In Syrian hamsters Mesocricetus auratus , a male that experiences a single episode of defeat will show submissive behaviors when faced with a smaller non-aggressive intruder within its own homecage Cooper et al. Finally, reduced social interaction behavior is reversed with chronic, but not acute, antidepressant treatment Kudryavtseva et al. These approaches to social defeat stress reliably induce anxiety-like and depression-like behaviors in males, and recently developed protocols have allowed for the study of effects of social defeat in both males and females. Abstract Stress is a major risk factor for the development of psychiatric disorders, such as depression, and the development of substance use disorder. This persistent phenotype resembles behavioral changes associated with depression and anxiety, which can linger for years. Here, we review the literature on sex differences and sex hormone regulation in innate immune cells in the lung in homeostasis and upon respiratory virus infection. Social defeat induces behavioral phenotypes related to depression and anxiety such as social withdrawal, submissive behavior, or anhedonia. While elegant studies have defined mechanistic roles for sex hormones and receptors in innate immune cells, much remains to be learned about the cellular and molecular mechanisms of action of ER, PR, and AR in myeloid cells and innate lymphocytes to promote the initiation and resolution of antiviral immunity in the lung. The publisher's final edited version of this article is available at J Neurosci Res See other articles in PMC that cite the published article. Although there are important sex differences in the prevalence of these disorders, the majority of preclinical models used to study stress induced disorders use males only. Social defeat stress has been shown to induce long-term changes in brain and behavior in both males and females. These disorders are frequently comorbid with substance use disorder Kessler et al. Humans show marked sex differences in the severity, prevalence, and outcome of inflammatory lung diseases including viral infection 2 , 3. Innate immune responses have crucial roles in early defense against viruses but also shape antigen-specific adaptive immune responses and promote tissue repair.
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