Corticosterone Administration to Promote Fear Memory Forgetting in an Animal Model of PTSD

摘要

It has been observed in normal subjects that forgetting is a spontaneous and/or gradual process in which previous memories are no longer readily retrievable from brain memory storage. The rate of forgetting is generally related to the function of time associated with an event initially experienced (Wixted 235-69). However, in PTSD patients, vivid flashbacks of traumatic memories occur even years after the traumatic incident, indicating that there is a failure of the forgetting process in the PTSD brain. Is there any way to promote the forgetting process in a PTSD subject. Emerging evidence suggests that systemic administration of corticosterone can enhance the memory forgetting process in animals and in healthy humans (de Quervain, Roozendaal, and McGaugh 787-90;Aerni et al. 1488-90). However, whether administration of corticosterone could also reduce fear memory flashbacks in PTSD patients and/or reduce the enhanced acoustic startle reflex observed in an animal model of PTSD, is currently unknown. We hypothesize that administration of corticosterone prior to or shortly after a period of intense, repeated stress will promote the traumatic memory forgetting process and/or prevent traumatic memory retrieval in our animal model of PTSD. Purpose: Our immediate objective is to use an animal model of PTSD developed in our laboratory to investigate the effectiveness of administration of corticosterone prior to or shortly after a period of intense, repeated stress in promoting the traumatic memory forgetting process and preventing fear memory retrieval. The use of a pharmacologic intervention to promote the memory forgetting process requires that it be introduced in an appropriate time window and in an optimized dose in order to obtain maximum efficacy without inducing adverse side effects.