Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation.
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 (1-40mg/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.
Blundell
Jacqueline
J
Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8813, USA.
Kouser
Mehreen
M
Powell
Craig M
CM
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004597:Electroshock; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes; D009433:Neural Inhibition / Q000502:physiology*; D011506:Proteins; D020123:Sirolimus / Q000494:pharmacology; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000503:physiopathology*; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D007166:Immunosuppressive Agents; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus