Preclinical assessment for selectively disrupting a traumatic memory via postretrieval inhibition of glucocorticoid receptors.
BACKGROUND
Traumatic experiences may lead to debilitating psychiatric disorders including acute stress disorder and posttraumatic stress disorder. Current treatments for these conditions are largely ineffective, and novel therapies are needed. A cardinal symptom of these pathologies is the reexperiencing of the trauma through intrusive memories and nightmares. Studies in animal models indicate that memories can be weakened by interfering with the postretrieval restabilization process known as memory reconsolidation. We previously reported that, in rats, intraamygdala injection of the glucocorticoid receptor antagonist RU38486 disrupts the reconsolidation of a traumatic memory. Here we tested parameters important for designing novel clinical protocols targeting the reconsolidation of a traumatic memory with RU38486.


METHODS
Using rat inhibitory avoidance, we tested the efficacy of postretrieval systemic administration of RU38486 on subsequent memory retention and evaluated several key preclinical parameters.


RESULTS
Systemic administration of RU38486 before or after retrieval persistently weakens inhibitory avoidance memory retention in a dose-dependent manner, and memory does not reemerge following a footshock reminder. The efficacy of treatment is a function of the intensity of the initial trauma, and intense traumatic memories can be disrupted by changing the time and number of interventions. Furthermore, one or two treatments are sufficient to disrupt the memory maximally. The treatment selectively targets the reactivated memory without interfering with the retention of another nonreactivated memory.


CONCLUSIONS
RU38486 is a potential novel treatment for psychiatric disorders linked to traumatic memories. Our data provide the parameters for designing promising clinical trials for the treatment of flashback-type symptoms of PTSD.
Taubenfeld
Stephen M
SM
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.
Riceberg
Justin S
JS
New
Antonia S
AS
Alberini
Cristina M
CM
D000375:Aging / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects*; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D013313:Stress Disorders, Post-Traumatic / Q000523:psychology*; D040701:Stress Disorders, Traumatic, Acute / Q000523:psychology*; D014947:Wounds and Injuries / Q000523:psychology*
D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone