Developing Memory Reconsolidation Blockers as Novel PTSD Treatments
Annual rept. 1 Jun 2010-31 May 2011
MASSACHUSETTS GENERAL HOSPITAL BOSTON
Pagination or Media Count:
So far this project has published the original finding that the anti-progesterone and glucocorticoid receptor antagonist mifepristone, when administered systemically, reduces reconsolidation of a cue-conditioned fear response in rats, and that the beta-adrenergic blocker propranolol blocks this mifepristone effect. We have produced the original discovery that alpha-2-adrenergic agonist clonidine also reduces reconsolidation of a cue-conditioned fear response in rats in a dose-dependent manner. We have produced the original discovery that the mammalian target of rapamycin mTOR kinase-dependent signaling mediates stabilization of fear conditioning-produced synaptic strengthening in the conditioned stimulus pathways following memory recall in rats, thus providing a postretrieval memory update mechanism. We have achieved steady progress in the implementation of two randomized, double-blind, placebo-controlled studies in humans one of post-reactivation mifepristone s ability to reduce psychophysiologic responding during traumatic imagery in trauma-exposed subjects, and the other of six sessions of post-reactivation propranolol for the treatment of PTSD. The blinds for these human studies have not yet been broken.