PMID- 21867718
OWN - NLM
STAT- MEDLINE
DCOM- 20120813
LR  - 20131121
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 62
IP  - 1
DP  - 2012 Jan
TI  - The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor 
      potentiator LY 451646 are preserved in bdnf(+)/(-) heterozygous null mice.
PG  - 391-7
LID - 10.1016/j.neuropharm.2011.08.015 [doi]
AB  - Accumulating evidence suggests that biogenic amine-based antidepressants act, at 
      least in part, via regulation of brain-derived neurotrophic factor (BDNF) 
      signaling. Biogenic amine-based antidepressants increase BDNF synthesis and 
      activate its signaling pathway through TrkB receptors. Moreover, the 
      antidepressant-like effects of these molecules are abolished in BDNF deficient 
      mice. Glutamate-based drugs, including the NMDA antagonist ketamine, and the AMPA 
      receptor potentiator LY 451646, mimic the effects of antidepressants in 
      preclinical tests with high predictive validity. In humans, a single intravenous 
      dose of ketamine produces an antidepressant effect that is rapid, robust and 
      persistent. In this study, we examined the role of BDNF in expression of the 
      antidepressant-like effects of ketamine and an AMPA receptor potentiator (LY 
      451646) in the forced swim test (FST). Ketamine and LY 451646 produced 
      antidepressant-like effects in the FST in mice at 45 min after a single 
      injection, but no effects were observed one week after a single ketamine 
      injection. As previously reported, the effects of imipramine in the forced swim 
      test were blunted in heterozygous BDNF knockout (bdnf(+/-)) mice. However 
      ketamine and LY 451646 produced similar antidepressant-like responses in wildtype 
      and bdnf(+/-) mice. Neither ketamine nor LY 451646 significantly influenced the 
      levels BDNF or TrkB phosphorylation in the hippocampus when assessed at 45 min or 
      7 days after the drug administration. These data demonstrate that under the 
      conditions tested, neither ketamine nor the AMPA-potentiator LY 451656 activate 
      BDNF signaling, but produce a characteristic antidepressant-like response in 
      heterozygous bdnf(+/-) mice. These data indicate that unlike biogenic amine-based 
      agents, BDNF signaling does not play a pivotal role in the antidepressant effects 
      of glutamate-based compounds. This article is part of a Special Issue entitled 
      'Anxiety and Depression'.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Lindholm, Jesse S O
AU  - Lindholm JS
AD  - Neuroscience Center, University of Helsinki, Helsinki, Finland.
FAU - Autio, Henri
AU  - Autio H
FAU - Vesa, Liisa
AU  - Vesa L
FAU - Antila, Hanna
AU  - Antila H
FAU - Lindemann, Lothar
AU  - Lindemann L
FAU - Hoener, Marius C
AU  - Hoener MC
FAU - Skolnick, Phil
AU  - Skolnick P
FAU - Rantamaki, Tomi
AU  - Rantamaki T
FAU - Castren, Eero
AU  - Castren E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110816
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (LY 404187)
RN  - 0 (Sulfonamides)
RN  - 690G0D6V8H (Ketamine)
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antidepressive Agents/*therapeutic use
MH  - Brain-Derived Neurotrophic Factor/*deficiency/metabolism
MH  - Depression/*drug therapy/genetics/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Exploratory Behavior/drug effects
MH  - Hippocampus/drug effects/metabolism
MH  - Imipramine/pharmacology/therapeutic use
MH  - Ketamine/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Reaction Time/drug effects/genetics
MH  - Receptor, trkA/metabolism
MH  - Sulfonamides/*pharmacology
MH  - Swimming/psychology
EDAT- 2011/08/27 06:00
MHDA- 2012/08/14 06:00
CRDT- 2011/08/27 06:00
PHST- 2011/04/28 00:00 [received]
PHST- 2011/08/09 00:00 [revised]
PHST- 2011/08/10 00:00 [accepted]
PHST- 2011/08/27 06:00 [entrez]
PHST- 2011/08/27 06:00 [pubmed]
PHST- 2012/08/14 06:00 [medline]
AID - S0028-3908(11)00348-0 [pii]
AID - 10.1016/j.neuropharm.2011.08.015 [doi]
PST - ppublish
SO  - Neuropharmacology. 2012 Jan;62(1):391-7. doi: 10.1016/j.neuropharm.2011.08.015. 
      Epub 2011 Aug 16.