Abstract
The study of fear conditioning has led to a better understanding of fear and anxiety-based disorders such as post-traumatic stress disorder (PTSD). Despite the fact many of these disorders are more common in women than in men, the vast majority of work investigating fear conditioning in rodents has been conducted in males. The goal of the work presented here was to better understand how biological sex affects contextual fear conditioning and expression. To this end, rats of both sexes were trained to fear a specific context and fear responses were measured upon re-exposure to the conditioning context. In the first experiment, male and female rats were given context fear conditioning and tested the next day during which freezing behavior was measured. In the second experiment, rats were trained and tested in a similar fashion while fear-potentiated startle and defecation were measured. We found that males showed more freezing behavior than females during a fear expression test. The expression of fear-potentiated startle did not differ between sexes, while males exhibited more defecation during a test in a novel context. These data suggest that the expression of defensive behavior differs between sexes and highlight the importance of using multiple measures of fear when comparing between sexes.
Highlights
The prevalence of some fear and anxiety-based psychopathologies differs between sexes, including post-traumatic stress disorder (PTSD), which is about twice as common in women as it is in men (Breslau et al, 1998; Kilpatrick et al, 2013)
There were no significant differences between males and females in fecal boli in Context A (U = 21, p > 0.05) or Context B (U = 28, p > 0.05). In this set of experiments male and female rats were given contextual fear conditioning and we measured different fear responses when rats were re-exposed to the context in which shock was delivered
Our results show that males exhibited higher levels of freezing compared to females when they were returned to the conditioning chamber a day following contextual fear conditioning
Summary
The prevalence of some fear and anxiety-based psychopathologies differs between sexes, including post-traumatic stress disorder (PTSD), which is about twice as common in women as it is in men (Breslau et al, 1998; Kilpatrick et al, 2013). The traumatic event that initiates the dysregulated fear response characteristic of PTSD is readily identifiable and is akin to a Pavlovian fear conditioning procedure with cues present at the time of trauma becoming associated with the traumatic experience (Parsons and Ressler, 2013). One hallmark of PTSD is that fear responses are not restricted to the cues present at the time of trauma, but instead generalize to stimuli not originally associated with trauma (Jovanovic et al, 2012; Kaczkurkin et al, 2017). Much of the ability to restrict fear responses to the appropriate stimuli has to do with the successful recognition of contextual cues (Maren et al, 2013). Studying contextual fear conditioning in rodents might offer some insight into this key aspect of PTSD.
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