Long-lasting memory abnormalities following exposure to the mouse defense test battery: An animal model of PTSD

• Memory dysfunctions play a crucial role in post-traumatic stress disorder.
• The long-term effects of traumatic stress on memory in mice were studied.
• Mice were confronted with a natural threat (a rat) in the defense test battery.
• Confrontation with the threat stimulus impaired memory 2 weeks after stress.
• Mice confronted with the rat and the MDTB context on day 14 had intact memory.

Memory dysfunctions are thought to play a crucial role both in the development and the maintenance of post-traumatic stress disorder (PTSD). Patients suffering from this condition persistently re-experience the traumatic event particularly when exposed to trauma-related cues and they display memory alterations. The objective of the present study was to investigate the long-term effects of a traumatic stress exposure on defensive behaviors and memory performance in mice confronted with a natural threat (i.e. a rat) in the defense test battery (MDTB), a procedure developed by the Blanchard group in the early nineties. The object recognition task, which addresses certain aspects of episodic memory, was used to assess the long-term consequences of stress on memory function. Mice were exposed to the MDTB followed two weeks later by a re-exposure to the test apparatus, but in the absence of the threat stimulus. Two hours after the second exposure to the MDTB apparatus, mice were exposed to the object recognition task (ORT). Another set of animals was used which were either exposed to the first or to the second MDTB session, before being tested in the ORT. Results showed that MDTB exposure produced long-lasting alterations in some defensive behaviors, such as escape attempts from the apparatus, which were increased during the re-exposure session at day 14 compared to non-exposed control mice. While exposure to the MDTB context only did not affect memory performance in the ORT, confrontation with the threat stimulus in the MDTB on day 1 impaired episodic memory two weeks after the stressful event. Finally, mice confronted both with the rat on day 1 and the MDTB context on day 14 displayed intact episodic memory performance in the ORT. We hypothesize that re-exposure to the context following a stressful event resulted in an increase of arousal, which subsequently led to an improvement in cognitive performance, a phenomenon also described in PTSD patients. The MDTB is a typical example of the tremendous efforts of Blanchard's lab to increase the translatability potential of the behavioral models of central nervous system disorders.