Accession Number:

ADA555352

Title:

Developing Memory Reconsolidation Blockers as Novel PTSD Treatments

Descriptive Note:

Annual rept. 1 Jun 2010-31 May 2011

Corporate Author:

MASSACHUSETTS GENERAL HOSPITAL BOSTON

Personal Author(s):

Report Date:

2011-06-01

Pagination or Media Count:

37.0

Abstract:

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.

Subject Categories:

  • Psychology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE