Will reconsolidation blockade offer a novel treatment for posttraumatic stress disorder?
Many articles about memory reconsolidation conclude with its therapeutic implications for posttraumatic stress disorder (PTSD). A core feature of PTSD is the memory of a traumatic event that is characterized by excessive strength, immalleability, and persistence. We found that Korean and World War II veterans with PTSD showed elevated physiological responses during mental imagery of their personal combat events as long as 40 years later. Recent animal research has challenged the permanence of consolidated memory traces by suggesting that reactivation (retrieval) of a memory can return it to an unstable state from which it must be re-consolidated if it is to persist. There is no reason to assume that if the therapeutic PTSD bomb can eventually beconstructed, its ultimate ingredient will be propranolol. In unpublished research with rats, we have found that the glucocorticoid receptor antagonist mifepristone, in addition to blocking reconsolidation of inhibitory avoidance learning (Taubenfeld et al., 2009), has substantially stronger cue-induced-fear reconsolidation-blocking properties than propranolol. This drug has yet to be tested in human reconsolidation experiments. Other drugs may exist that are stronger still. However, for any drug to be clinically useful, it must be approved for human use and capable of systemic administration. Moreover, the efficacy of any drug has yet to be compared with the efficacy of behavioral memory updating techniques. All these questions and more will need to be addressed within a large research and development Manhattan project for PTSD. The translation from preclinical work to clinical application may prove long and difficult, and even unsuccessful. However, given the importance of PTSD as a public mental health problem, it is worth pursuing.
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