PMID- 25746515
OWN - NLM
STAT- MEDLINE
DCOM- 20160104
LR  - 20211203
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 286
DP  - 2015 Jun 1
TI  - Time-dependent effects of rapamycin on consolidation of predator stress-induced 
      hyperarousal.
PG  - 104-11
LID - S0166-4328(15)00134-5 [pii]
LID - 10.1016/j.bbr.2015.02.045 [doi]
AB  - Previous studies have indicated that rapamycin, a potent inhibitor of the 
      mammalian target of rapamycin (mTOR) pathway, blocks consolidation of 
      shock-induced associative fear memories. Moreover, rapamycin's block of 
      associative fear memories is time-dependent. It is unknown, however, if rapamycin 
      blocks consolidation of predator stress-induced non-associative fear memories. 
      Furthermore, the temporal pattern of mTOR activation following predator stress is 
      unknown. Thus, the goal of the current studies was to determine if rapamycin 
      blocks consolidation of predator stress-induced fear memories and if so, whether 
      rapamycin's effect is time-dependent. Male rats were injected systemically with 
      rapamycin at various time points following predator stress. Predator stress 
      involves an acute, unprotected exposure of a rat to a cat, which causes 
      long-lasting non-associative fear memories manifested as generalized hyperarousal 
      and increased anxiety-like behaviour. We show that rapamycin injected immediately 
      after predator stress blocked consolidation of stress-induced startle. However, 
      rapamycin injected 9, 24 or 48h post predator stress potentiated stress-induced 
      startle. Consistent with shock-induced associative fear memories, we show that 
      mTOR signalling is essential for consolidation of predator stress-induced 
      hyperarousal. However, unlike shock-induced fear memories, a second, persistent, 
      late phase mTOR-dependent process following predator stress actually dampens 
      startle. Consistent with previous findings, our data support the potential role 
      for rapamycin in treatment of stress related disorders such as posttraumatic 
      stress disorder. However, our data suggest timing of rapamycin administration is 
      critical.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Fifield, Kathleen
AU  - Fifield K
AD  - Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave. 
      , St. John's, Newfoundland, Canada A1B 3X9.
FAU - Hebert, Mark
AU  - Hebert M
AD  - Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave. 
      , St. John's, Newfoundland, Canada A1B 3X9.
FAU - Williams, Kimberly
AU  - Williams K
AD  - Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave. 
      , St. John's, Newfoundland, Canada A1B 3X9.
FAU - Linehan, Victoria
AU  - Linehan V
AD  - Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave. 
      , St. John's, Newfoundland, Canada A1B 3X9.
FAU - Whiteman, Jesse D
AU  - Whiteman JD
AD  - Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave. 
      , St. John's, Newfoundland, Canada A1B 3X9.
FAU - Mac Callum, Phillip
AU  - Mac Callum P
AD  - Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave. 
      , St. John's, Newfoundland, Canada A1B 3X9.
FAU - Blundell, Jacqueline
AU  - Blundell J
AD  - Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave. 
      , St. John's, Newfoundland, Canada A1B 3X9. Electronic address: jblundell@mun.ca.
LA  - eng
GR  - ROP 91548/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150305
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Psychotropic Drugs)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Arousal/drug effects/physiology
MH  - Body Weight/drug effects
MH  - Cats
MH  - Male
MH  - Memory Consolidation/*drug effects/physiology
MH  - Predatory Behavior
MH  - Psychotropic Drugs/*pharmacology
MH  - Random Allocation
MH  - Rats, Long-Evans
MH  - Reflex, Startle/drug effects/physiology
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - Stress, Psychological/*drug therapy/*physiopathology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Time Factors
OTO - NOTNLM
OT  - Consolidation
OT  - Hyperarousal
OT  - Predator stress
OT  - Rapamycin
OT  - Startle
OT  - mTOR
EDAT- 2015/03/10 06:00
MHDA- 2016/01/05 06:00
CRDT- 2015/03/10 06:00
PHST- 2014/07/14 00:00 [received]
PHST- 2015/02/19 00:00 [revised]
PHST- 2015/02/24 00:00 [accepted]
PHST- 2015/03/10 06:00 [entrez]
PHST- 2015/03/10 06:00 [pubmed]
PHST- 2016/01/05 06:00 [medline]
AID - S0166-4328(15)00134-5 [pii]
AID - 10.1016/j.bbr.2015.02.045 [doi]
PST - ppublish
SO  - Behav Brain Res. 2015 Jun 1;286:104-11. doi: 10.1016/j.bbr.2015.02.045. Epub 2015 
      Mar 5.