Sex differences in long-term fear and anxiety-like responses in a preclinical model of PTSD

With a high prevalence of posttraumatic stress disorder (PTSD) in females, studying sex differences in preclinical models is of substantial importance. We have previously employed behavioural criteria to identify and characterize a subpopulation of rats that presented impaired fear extinction and long-term fear and anxiety responses following fear conditioning. We now exposed male and female rats to fear conditioning and extinction and segregated the animals into weak-(WE) and strong-extinction (SE) groups based on behavioural scores during extinction. Animals were subsequently tested for tone and context recall, as well as anxiety-like responses in the marble burying and novelty suppression of feeding (NSF) tests. Vaginal lavages were collected to characterize the phase of the estrous cycle during fear extinction. We found that females had reduced freezing during tone recall and a lower latency to feed in the NSF test. No differences were found in females undergoing extinction during high and low estrogen phases of the cycle in any of the performed tests. Overall, the percentage of animals that presented WE and SE phenotypes was similar in males and females. Both, WE males and females had increased freezing during tone and context recall. Along with our previous reports, WE males presented anxiety-like responses, particularly in the NSF compared to SE animals. In contrast, WE females buried less marbles than their SE mates. Future investigation including a larger number of behavioural tests are certainly required to corroborate our findings and ascertain potential mechanisms to explain the differences observed in our study.

Automated summary

Studying sex differences in preclinical models of posttraumatic stress disorder (PTSD) is significantly important. The study observed that female rats exposed to fear conditioning and extinction displayed reduced freezing during tone recall and a lower latency to feed in the novelty suppression of feeding (NSF) test. The different estrogen phases of the cycle did not affect the extinction performance of female rats. WE males and females showed increased freezing during tone and context recall, while WE males exhibited anxiety-like responses in the NSF test compared to SE animals. WE females buried fewer marbles than their SE counterparts. Further investigation is needed to validate these findings and understand the underlying mechanisms.