Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation

Jacqueline Blundell, Mehreen Kouser, Craig M. Powell

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Background: Established traumatic memories have a selective vulnerability to pharmacologic interventions following their reactivation that can decrease subsequent memory recall. This vulnerable period following memory reactivation is termed reconsolidation. The pharmacology of traumatic memory reconsolidation has not been fully characterized despite its potential as a therapeutic target for established, acquired anxiety disorders including posttraumatic stress disorder (PTSD). The mammalian target of rapamycin (mTOR) kinase is a critical regulator of mRNA translation and is known to be involved in various forms of synaptic plasticity and memory consolidation. We have examined the role of mTOR in traumatic memory reconsolidation. Methods: Male C57BL/6 mice were injected systemically with the mTOR inhibitor rapamycin (1-40 mg/kg), at various time points relative to contextual fear conditioning training or fear memory retrieval, and compared to vehicle or anisomycin-treated groups (N = 10-12 in each group). Results: Inhibition of mTOR via systemic administration of rapamycin blocks reconsolidation of an established fear memory in a lasting manner. This effect is specific to reconsolidation as a series of additional experiments make an effect on memory extinction unlikely. Conclusions: Systemic rapamycin, in conjunction with therapeutic traumatic memory reactivation, can decrease the emotional strength of an established traumatic memory. This finding not only establishes mTOR regulation of protein translation in the reconsolidation phase of traumatic memory, but also implicates a novel, FDA-approved drug treatment for patients suffering from acquired anxiety disorders such as PTSD and specific phobia.

Original languageEnglish (US)
Pages (from-to)28-35
Number of pages8
JournalNeurobiology of Learning and Memory
Volume90
Issue number1
DOIs
StatePublished - Jul 2008

Fingerprint

Sirolimus
Fear
Protein Biosynthesis
Post-Traumatic Stress Disorders
Anxiety Disorders
Inhibition (Psychology)
TOR Serine-Threonine Kinases
Anisomycin
Neuronal Plasticity
Inbred C57BL Mouse
Phosphotransferases
Therapeutics
Pharmacology

Keywords

  • Consolidation
  • Extinction
  • Fear conditioning
  • Learning and memory
  • mTOR
  • Posttraumatic stress disorder
  • Rapamycin
  • Reconsolidation

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Experimental and Cognitive Psychology

Cite this

Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. / Blundell, Jacqueline; Kouser, Mehreen; Powell, Craig M.

In: Neurobiology of Learning and Memory, Vol. 90, No. 1, 07.2008, p. 28-35.

Research output: Contribution to journalArticle

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