, 2013). Collectively, findings from these studies do not paint a fully consistent picture, again emphasizing the specificity with which stressful events can affect the brain, and the care required in experimental design for future studies. In particular, it may be the case that certain stress models are more ethologically relevant to females vs. males—for example, social stress vs. predator exposure. One of the primary issues of interpretation in studies that employ a “stress vs. no stress” group design, however, is

whether the changes observed in the stress group as a whole accurately represent the disease state, or simply the normal adaptations the brain undergoes in response to trauma (Cohen et al., 2004). As SB203580 in vivo noted in the introduction, PTSD occurs in a limited subset of trauma-exposed individuals, and approaches that instead examine individual stress responses in order to identify resilient and susceptible subpopulations are becoming a new standard for animal models of mental illness (Krishnan, 2014). ABT737 One paradigm that has been especially fruitful has been the resident-intruder social defeat model, in which mice are repeatedly exposed to a dominant aggressor (Miczek, 1979). After chronic social defeat, mice reliably stratify on measures of social interaction when exposed to an unfamiliar mouse, distinctions

that can then be used to examine biological markers of susceptible (anti-social) and resilient (social) populations (Golden et al., 2011), (Gómez-Lázaro et al., 2011), (Elliott et al., 2010). The relationship of resilient vs. susceptible phenotypes

to learned fear behavior has recently begun to be studied, but a clear picture has not yet emerged: Chou et al. (2014) found that susceptible mice exhibited greater freezing during fear conditioning compared to a resilient population, while Meduri et al. (2013) previously reported that resilient animals expressed higher and longer-sustained fear levels. Potential sex differences in social defeat resilience are not known, primarily Levetiracetam because common laboratory strains of female rodents do not typically display territorial aggression in the same way males do. There are several exceptions worth noting, however. First is the female California mouse, and Trainor and colleagues have used this model to identify a number of sex differences in the behavioral and cellular changes that social defeat elicits (Greenberg et al., 2014 and Trainor et al., 2011), including an intriguing role for dopaminergic signaling (Campi et al., 2014). To date, however, this model has not been used to identify susceptible and resilient populations of females. A second model modifies the classic male resident-intruder paradigm, taking advantage of the aggression that a lactating female rat will express to an intruder female.