ABSTRACT
Symptoms of trauma and stressor related disorders such as post-traumatic stress disorder (PTSD) often develop well after the traumatic experience has occurred, and so identifying early predictors of risk or resilience is important for the implementation of interventional therapies. For example, passive coping strategies such as tonic immobility and peritraumatic dissociation during the trauma itself are risk factors for the developments of PTSD, especially in women. However, discrete, sex-specific coping responses that predict later outcomes in animal models have not been rigorously defined. Recently, we identified an active, escape-like response exhibited primarily by a subset of female rats in a classic auditory fear conditioning task ("darting"). Here, we asked whether darting during conditioning predicted active responding in a single forced swim (SFS) session to study the potential for darting to reflect a trait-like behavioral strategy that translated across stress models. Male and female Sprague-Dawley (SD) rats were tested in auditory fear conditioning acquisition and memory tests to identify Darters, and then a 15-min SFS 2 weeks later. We observed a significant effect of sex in conditioned freezing behavior, with males exhibiting greater freezing than females across conditioning and testing trials in comparison to females. However, females demonstrated higher velocities in response to shock presentations, and were more likely to exhibit darting behavior in response to the conditioned stimulus (CS). In SFS measures, females engaged in active behaviors such as climbing, head shaking, and diving in greater proportions than males, while males spent more time immobile throughout testing. Despite females exhibiting a more diverse behavioral repertoire in both tests, Darters did not differ from Non-darters in any SFS measure. These results suggest that the propensity to dart does not reflect a simple hyperactivity, and that despite conceptual overlap across the two tests (inescapable stress exposure and the ability to measure active vs. passive coping), the behavioral strategies engaged by an individual animal in each are likely driven by discrete mechanisms. We discuss potential challenges in interpretation of standard behavioral outcomes in classic models across the sexes, and consider the potential need for novel models that better tap into motivational states in females.
ABSTRACT
Women are twice as likely as men to suffer from trauma- and stressor-related disorders. The development of improved therapeutic interventions is contingent upon a more complete grasp of both the neural and behavioral dynamics of the stress response in females. The rodent forced swim test (FST) is a valuable animal model for exploring the neurobiological mechanisms responsible for selection of active and passive responses to inescapable stressors, but it is often neglected in 2-day FST studies is the dissociation of innate (Day 1) versus learned (Day 2) coping responses. Here, we used a modified, long-term (4-week) FST paradigm and immunohistological analysis to study the interactions of sex, strain, and housing arrangement on selection of active and passive coping strategies in Sprague Dawley (SD) and Long Evans (LE) rats. We observed significant strain × sex interactions in both forced swim sessions with respect to both passive (immobility) and active (climbing and headshakes) responses. In immobility measures, we observed stable sex differences in SD rats and a stable lack of sex differences in LE rats across tests. In addition, both SD and LE females displayed significantly more headshakes than males during Test 1 and more climbing in Test 2. Most notably, males, but not females, exhibited a cross-test increase in immobility, suggesting that males and females may engage different learning processes in a 2-day FST. These sex differences corresponded to c-fos expression in the medial prefrontal cortex (mPFC), indicating that the mPFC may contribute to sexually dimorphic behavior in the FST. (PsycINFO Database Record
