Hyperarousal does not depend on trauma-related contextual memory in an animal model of Posttraumatic Stress Disorder

Both classical fear conditioning and fear sensitization have been implicated in the development of Posttraumatic Stress Disorder (PTSD), but little is known about their interaction or interdependency. Therefore, we administered the NMDA receptor antagonist AP5 or vehicle bilaterally into the dorsal hippocampus of C57BL/6N mice 15 min before administration of an electric footshock. One month later mice were tested for their conditioned fear reaction to the shock context (associative fear memory) and for their sensitized fear response to a neutral tone in a new context (hyperarousal). AP5-treated animals exhibited only half as much conditioned, but equal amounts of sensitized fear, compared to vehicle-treated mice, demonstrating that hyperarousal does not depend on associative fear memory about the aversive encounter, but solely on sensitization induced by the inescapable footshock. This result points to the need for a ‘desensitization’ approach in PTSD therapy, as sensitization and classical conditioning seem to be independent processes in this psychiatric disorder.