Examining associative and non-associative fear memories in the Rat Exposure Test

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating psychological condition which results in a variety of negative symptoms causing significant functional impairment. These symptoms fall into four clusters: avoidance, intrusion, negative cognitions or mood, and changes in arousal. Among those who actively seek treatment for PTSD, only 30% achieve full remission. This disparity represents a need for further research into therapies for PTSD. Predator stress is an animal model of PTSD which exposes a prey animal to a natural predator, creating a situation in which the animal fears imminent injury or death. The rat exposure test (RET) developed by Yang et al. (2004) has been successful in producing defensive behaviors in the mouse during a 5-minute protected exposure to a rat. Long-lasting behavioral changes in the mice, however, have not been assessed in this paradigm. Thus, the goal of these studies was to better assess the RET as a model of PTSD. Experiment 1 examined whether the effects of the RET could be seen up to three weeks post-exposure. The results from this experiment revealed that associative, but not non-associative fear, could be seen up to 21 days post-exposure. Specifically, predator-stressed (PS) animals froze significantly more than control animals upon re-exposure to the fear context. There were no differences observed in non-associative fear memories as measured in the elevated plus maze (EPM), open field (OF), or light/dark (LD) box. After minor changes to the RET protocol were made, the results from Experiment 2 demonstrated that the RET produced associative and non-associative fear memories. Specifically, PS animals froze significantly more than controls during re-exposure to the fear context. In addition, PS animals showed increased anxiety-like behavior in the EPM and LD tests. Finally, Experiment 3 tested the effects of the RET in female mice, as well as duration of the RET (5 min versus 60 min). The results indicated that there were no differences between PS and control animals regardless of length of exposure. Collectively, these results indicate more refinement needs to be made to the RET to achieve consistent, robust results across experiments.