Evaluating social defeat as a model for psychopathology in adult female rodents

Abstract

Social conflict is a predominant stressor in humans and is associated with increased risk for developing psychological illnesses including depression and anxiety. Overwhelmingly, more women suffer from these disorders, which may be due to increased stress sensitivity. Like humans, rodents experience a myriad of physiological and behavioral sequelae due to prolonged stress exposure. Although the motivation for social conflict may differ between humans and rodents, female rodents may provide an opportunity to explore the underlying mechanisms by which stress confers risk for psychopathology in women. Because most female rodents do not express spontaneous aggression, the majority of basic research examines the physiological and behavioral outcomes of social conflict in male rodents. However, there are instances where female rodents exhibit territorial (California mice and Syrian hamsters) and maternal aggression (rats, mice, and hamsters) creating a venue to examine sex differences in physiology and behavior in response to stress. While many studies rely upon nonsocial behavioral assays (e.g., elevated plus maze, forced swim test) to assess the impact of stress on emotionality, here we primarily focus on behavioral outcomes in social-based assays in rodents. This is critically important given that disruptions in social relationships can be a cause and consequence of neuropsychiatric diseases. Next, we briefly discuss how sex differences in the recruitment of neural circuitry and/or neurochemistry in response to stress may underlie sex differences in neuroendocrine and behavioral stress responses. Finally, the translational value of females in rodent stress models and considerations regarding behavioral interpretations of these models are discussed. V C 2016 Wiley Periodicals, Inc.

Acute stress induces long-lasting alterations in the dopaminergic system of female mice

“…While these immediate physiological and cognitive responses may be adaptive, stress exposure, when chronic or severe, can cause long-lasting alterations in brain structure and function, which can translate into maladaptive behaviors later in life (Chetty et al, 2014; Koenig et al, 2011; Mah et al, 2016; McEwen et al, 2015; Schneiderman et al, 2005). For example, stress is associated with a number of negative outcomes experienced in adulthood, including an increased risk in the development of several neuropsychiatric disorders (e.g., addiction, depression, anxiety, and schizophrenia) (Mah et al, 2016; Piazza and Le Moal, 1998; Solomon, 2017). Although stress and mental health disorders appear to be consistently linked, the effects of stress on subsequent disease-relevant behaviors have been distressingly understudied in females (Goel and Bale, 2009).…”

“…Impairments in social behavior represent a hallmark feature in a number of neuropsychiatric diseases, including depression, anxiety and schizophrenia. Although many factors contribute to the development of mood disorders, as stated above, stress can trigger the onset and increase the risk for the development of these disorders (Mah et al, 2016; Piazza and Le Moal, 1998; Solomon, 2017). Stress, especially when chronic, can reduce social motivation and interactions in a variety of tests (Sandi and Haller, 2015), however a challenge is that many of the studies examining the effects of stress on social behavior use a social defeat stressor (Cao et al, 2010; Chaudhury et al, 2013; Krishnan et al, 2007), leaving the question of whether non-social stressors can alter social behavior unanswered.…”

Social defeat models in animal science: What we have learned from rodent models

“…Recently, variations of the social defeat model, including a juvenile model and a female model have been reported (Iñiguez et al . ; Solomon ), and analysis of these models will enable us to gain a better understanding of stress‐induced abnormal behaviors and psychiatric disorders such as depression.…”

“…Since it has previously been described that aggressive ICR mice constantly attack B6 mice in less than 50% of encounters (Golden et al 2011), it is important to conduct selection of aggressive residents before performing the CSDS paradigm, in order to produce a successful CSDS model. Recently, variations of the social defeat model, including a juvenile model and a female model have been reported (Iñiguez et al 2014;Solomon 2017), and analysis of these models will enable us to gain a better understanding of stress-induced abnormal behaviors and psychiatric disorders such as depression.…”

Sex/gender influences on the nervous system: Basic steps toward clinical progress

“…non-human primate behavioral development (Lonsdorf, 2017), and Translational value of female rodent social stress models: Are we missing the mark? (Solomon, 2017) explore the use of animal models in various areas of neuroscience and the challenges posed in translation to humans in biomedical research.…”