Preclinical Assessment for Selectively Disrupting a Traumatic Memory via Postretrieval Inhibition of Glucocorticoid Receptors

Stephen M. Taubenfeld, Justin S. Riceberg, Antonia S. New, Cristina Alberini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalBiological Psychiatry
Volume65
Issue number3
DOIs
StatePublished - Feb 1 2009

Fingerprint

Glucocorticoid Receptors
Post-Traumatic Stress Disorders
Inhibition (Psychology)
Psychiatry
Therapeutics
Stress Disorders, Traumatic, Acute
Wounds and Injuries
Clinical Protocols
Animal Models
Clinical Trials

Keywords

  • Fear conditioning
  • glucocorticoid receptor
  • inhibitory avoidance
  • memory
  • PTSD
  • reconsolidation
  • RU38486

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Preclinical Assessment for Selectively Disrupting a Traumatic Memory via Postretrieval Inhibition of Glucocorticoid Receptors. / Taubenfeld, Stephen M.; Riceberg, Justin S.; New, Antonia S.; Alberini, Cristina.

In: Biological Psychiatry, Vol. 65, No. 3, 01.02.2009, p. 249-257.

Research output: Contribution to journalArticle

@article{032a08f50e2b4b3bab65a11655fb914b,
title = "Preclinical Assessment for Selectively Disrupting a Traumatic Memory via Postretrieval Inhibition of Glucocorticoid Receptors",
abstract = "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.",
keywords = "Fear conditioning, glucocorticoid receptor, inhibitory avoidance, memory, PTSD, reconsolidation, RU38486",
author = "Taubenfeld, {Stephen M.} and Riceberg, {Justin S.} and New, {Antonia S.} and Cristina Alberini",
year = "2009",
month = "2",
day = "1",
doi = "10.1016/j.biopsych.2008.07.005",
language = "English (US)",
volume = "65",
pages = "249--257",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "3",

}

TY - JOUR

T1 - Preclinical Assessment for Selectively Disrupting a Traumatic Memory via Postretrieval Inhibition of Glucocorticoid Receptors

AU - Taubenfeld, Stephen M.

AU - Riceberg, Justin S.

AU - New, Antonia S.

AU - Alberini, Cristina

PY - 2009/2/1

Y1 - 2009/2/1

N2 - 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.

AB - 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.

KW - Fear conditioning

KW - glucocorticoid receptor

KW - inhibitory avoidance

KW - memory

KW - PTSD

KW - reconsolidation

KW - RU38486

UR - http://www.scopus.com/inward/record.url?scp=58149313654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149313654&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2008.07.005

DO - 10.1016/j.biopsych.2008.07.005

M3 - Article

VL - 65

SP - 249

EP - 257

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 3

ER -