, 2010), but the reasons for this discrepancy are poorly understood. This is a particularly topical problem in the context of our recent wars in the Middle East, which have been fought by a greater percentage of women than have any international

conflicts before them (D. of Defense, 2008)). Women are the fastest growing population in US Veterans Affairs (VA) hospitals, and the current percentage of female patients at VA hospitals is expected to double in the next twenty-five Venetoclax solubility dmso years (Yano et al., 2010). Women who suffer from PTSD undoubtedly will be best served by treatments that take into consideration not only the unique experiences of a woman in combat (e.g. the disproportionately high incidence of Military Sexual Trauma in women (Himmelfarb et al., 2006)), but also the distinct neurobiological background against which those experiences take place. It is thus all the more imperative that the biological ramifications of stress in women are better understood, and that sex-specific markers of susceptibility and resilience to stress-related mental health problems are identified. For decades, the use of animal models in preclinical research has provided great insight into the neural circuits and mechanisms that mediate the effects of stress. However, despite the twofold increase in PTSD prevalence in women, the vast majority of relevant basic science

work has been conducted in male animals (Lebron-Milad and Milad, 2012). We are thus left with a poor picture of stress effects Quizartinib order that

are specific to the female brain, knowledge of which could aid in the development of better treatments. Perhaps even more concerning is the lack of a behavioral model that convincingly first produces sex differences that mirror those observed in humans—i.e., one in which females reliably exhibit PTSD-like symptoms more robustly and frequently than males do (Kokras and Dalla, 2014). This fundamental lack of agreement between animal and human populations may be due to the fact that the common paradigms used to measure fear and anxiety were developed using male animals. Inconsistencies observed when females are evaluated using these tools may indicate that the traditional outcome measures associated with each test in fact tap into distinct processes in females, and do not accurately reflect the emotional states assumed based on data collected in males. In this review, we will examine evidence from studies of sex differences in stress effects on classic behavioral fear learning paradigms. Ultimately, our goal is to identify measures that may require re-interpretation or adjustments in design, so that sex-specific markers of resilience and susceptibility to stress may be more accurately determined. PTSD is characterized by a strong and persistent association between the memory of the trauma and its associated cues, such that the cues alone can trigger a fear response (Rothbaum and Davis, 2003).