PMID- 25231918
OWN - NLM
STAT- MEDLINE
DCOM- 20150612
LR  - 20211021
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 232
IP  - 4
DP  - 2015 Feb
TI  - Anxiolytic effects of ketamine in animal models of posttraumatic stress disorder.
PG  - 663-72
LID - 10.1007/s00213-014-3697-9 [doi]
AB  - This study investigated the effectiveness of ketamine, a noncompetitive 
      N-methyl-D-aspartate (NMDA) receptor antagonist, in alleviating the enhanced 
      anxiety and fear response in both a mouse model of PTSD induced by inescapable 
      electric foot shocks and a rat model of PTSD induced by a time-dependent 
      sensitization (TDS) procedure. First, we evaluated the effect of ketamine on 
      behavioral deficits in a mouse model of PTSD that consisted of foot shocks 
      followed by three situational reminders. Our results showed that the aversive 
      procedure induced several behavioral deficiencies, such as increased freezing 
      behavior and anxiety, as well as reduced time spent in an aversive-like context, 
      which were reversed by repeated treatment with ketamine. The effect of ketamine 
      on behavioral changes after exposure to TDS was also investigated, and the levels 
      of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured. The 
      results revealed that after TDS, the rats showed a significant increase in 
      contextual freezing and a decrease in the percentage of time spent in and numbers 
      of entries into open arms in the elevated plus maze test. As a positive control 
      drug, sertraline (Ser, 15 mg/kg, i.g.), a selective serotonin reuptake inhibitor 
      (SSRI) ameliorated these behavioral deficits. These behavioral effects were 
      mimicked by chronic ketamine treatment. Furthermore, ketamine normalized the 
      decreased BDNF level in the hippocampus in post-TDS rats. Taken together, these 
      results suggest that ketamine exerts a therapeutic effect on PTSD that might be 
      at least partially mediated by an influence on BDNF signaling in the hippocampus.
FAU - Zhang, Li-Ming
AU  - Zhang LM
AD  - Department of New Drug Evaluation, Beijing Institute of Pharmacology and 
      Toxicology, 27 Taiping Road, Haidian, Beijing, 100850, China.
FAU - Zhou, Wen-Wen
AU  - Zhou WW
FAU - Ji, Ya-Jun
AU  - Ji YJ
FAU - Li, Ying
AU  - Li Y
FAU - Zhao, Nan
AU  - Zhao N
FAU - Chen, Hong-Xia
AU  - Chen HX
FAU - Xue, Rui
AU  - Xue R
FAU - Mei, Xin-Guo
AU  - Mei XG
FAU - Zhang, You-Zhi
AU  - Zhang YZ
FAU - Wang, Heng-Lin
AU  - Wang HL
FAU - Li, Yun-Feng
AU  - Li YF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140918
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Anti-Anxiety Agents/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Disease Models, Animal
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Hippocampus/drug effects/metabolism
MH  - Ketamine/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stress Disorders, Post-Traumatic/*drug therapy/metabolism
EDAT- 2014/09/19 06:00
MHDA- 2015/06/13 06:00
CRDT- 2014/09/19 06:00
PHST- 2013/12/10 00:00 [received]
PHST- 2014/07/28 00:00 [accepted]
PHST- 2014/09/19 06:00 [entrez]
PHST- 2014/09/19 06:00 [pubmed]
PHST- 2015/06/13 06:00 [medline]
AID - 10.1007/s00213-014-3697-9 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2015 Feb;232(4):663-72. doi: 
      10.1007/s00213-014-3697-9. Epub 2014 Sep 18.