Developing Memory Reconsolidation Blockers as Novel PTSD Treatments
Abstract
So far this project has produced 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. This has been demonstrated in two independent laboratories. We have produced the further original discovery that the beta-adrenergic blocker propranolol blocks this mifepristone effect. We have produced the further original discoveries that systemic administration of the synthetic cannabinoid nabilone, the posterior peptide hormone oxytocin, the anti-dopaminergic drug haloperidol, and the protein synthesis inhibitor rapamycin all reduce reconsolidation of a cue-conditioned fear response in rats, although none of these is as powerful as mifepristone. We have produced the further original discovery that postreactivation rapamycin reduces synaptic strength underlying auditory fear conditioning. We have discovered input timing-dependent plasticity in auditory fear conditioning. We have successfully launched a randomized, double-blind controlled study of six sessions of post-reactivation propranolol for the treatment of PTSD, and a pilot study of post-reactivation mifepristone's ability to reduce psychophysiologic responding during traumatic imagery in trauma-exposed human subjects. We conclude that animal and human studies show promise for the development of a novel treatment for PTSD based upon pharmacological blockade of memory reconsolidation. However, we are still a long way from demonstrating that any such treatment is efficacious.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2010
- Accession Number
- ADA540931
Entities
People
- Alain Brunet
- Karim Nader
- Roger K. Pitman
- Vadim Y. Bolshakov