PMID- 25539510
OWN - NLM
STAT- MEDLINE
DCOM- 20150930
LR  - 20220318
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Print)
IS  - 1461-1457 (Linking)
VI  - 18
IP  - 1
DP  - 2014 Oct 31
TI  - BDNF release is required for the behavioral actions of ketamine.
LID - pyu033 [pii]
LID - 10.1093/ijnp/pyu033 [doi]
AB  - BACKGROUND: Recent studies demonstrate that the rapid antidepressant ketamine 
      increases spine number and function in the medial prefrontal cortex (mPFC), and 
      that these effects are dependent on activation of glutamate 
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and 
      brain-derived neurotrophic factor (BDNF). In vitro studies also show that 
      activation of AMPA receptors stimulates BNDF release via activation of L-type 
      voltage-dependent calcium channels (VDCC). METHODS: Based on this evidence, we 
      examined the role of BDNF release and the impact of L-type VDCCs on the 
      behavioral actions of ketamine. RESULTS: The results demonstrate that infusion of 
      a neutralizing BDNF antibody into the mPFC blocks the behavioral effects of 
      ketamine in the forced swim test (FST). In addition, we show that pretreatment 
      with nifedipine or verapamil, two structurally-different L-type calcium channel 
      antagonists, blocks the behavioral effects of ketamine in the FST. Finally, we 
      show that ketamine treatment stimulates BDNF release in primary cortical neurons 
      and that this effect is blocked by inhibition of AMPA receptors or L-type VDCCs. 
      CONCLUSIONS: Taken together, these results indicate that the antidepressant 
      effects of ketamine are mediated by activation of L-type VDCCs and the release of 
      BDNF. They further elucidate the cellular mechanisms underlying this novel 
      rapid-acting antidepressant.
CI  - (c) The Author 2014. Published by Oxford University Press on behalf of CINP.
FAU - Lepack, Ashley E
AU  - Lepack AE
AD  - Departments of Psychiatry and Neurobiology, Yale University School of Medicine, 
      New Haven, CT (Drs Lepack, Fuchikami, Dwyer, Banasr, and Duman).
FAU - Fuchikami, Manabu
AU  - Fuchikami M
AD  - Departments of Psychiatry and Neurobiology, Yale University School of Medicine, 
      New Haven, CT (Drs Lepack, Fuchikami, Dwyer, Banasr, and Duman).
FAU - Dwyer, Jason M
AU  - Dwyer JM
AD  - Departments of Psychiatry and Neurobiology, Yale University School of Medicine, 
      New Haven, CT (Drs Lepack, Fuchikami, Dwyer, Banasr, and Duman).
FAU - Banasr, Mounira
AU  - Banasr M
AD  - Departments of Psychiatry and Neurobiology, Yale University School of Medicine, 
      New Haven, CT (Drs Lepack, Fuchikami, Dwyer, Banasr, and Duman).
FAU - Duman, Ronald S
AU  - Duman RS
AD  - Departments of Psychiatry and Neurobiology, Yale University School of Medicine, 
      New Haven, CT (Drs Lepack, Fuchikami, Dwyer, Banasr, and Duman). 
      ronald.duman@yale.edu.
LA  - eng
GR  - R01 MH093897/MH/NIMH NIH HHS/United States
GR  - R01 MH105910/MH/NIMH NIH HHS/United States
GR  - MH093897/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141031
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Receptors, AMPA)
RN  - 690G0D6V8H (Ketamine)
RN  - CJ0O37KU29 (Verapamil)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
EIN - Int J Neuropsychopharmacol. 2016 Apr 27;:. PMID: 27207904
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels, L-Type/metabolism
MH  - Cells, Cultured
MH  - Depressive Disorder/drug therapy/physiopathology
MH  - Ketamine/*pharmacology
MH  - Male
MH  - Neurons/drug effects/physiology
MH  - Nifedipine/pharmacology
MH  - Prefrontal Cortex/drug effects/physiopathology
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/antagonists & inhibitors/metabolism
MH  - Verapamil/pharmacology
PMC - PMC4368871
MID - NIHMS686432
OTO - NOTNLM
OT  - BDNF
OT  - L-type VDCC
OT  - depression
OT  - glutamate
OT  - ketamine
EDAT- 2014/12/30 06:00
MHDA- 2015/10/01 06:00
PMCR- 2014/12/19
CRDT- 2014/12/25 06:00
PHST- 2014/12/25 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/10/01 06:00 [medline]
PHST- 2014/12/19 00:00 [pmc-release]
AID - pyu033 [pii]
AID - 10.1093/ijnp/pyu033 [doi]
PST - epublish
SO  - Int J Neuropsychopharmacol. 2014 Oct 31;18(1):pyu033. doi: 10.1093/ijnp/pyu033.