PMID- 25560757
OWN - NLM
STAT- MEDLINE
DCOM- 20160303
LR  - 20181113
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 20
IP  - 3
DP  - 2015 Mar
TI  - Rapid antidepressants stimulate the decoupling of GABA(B) receptors from 
      GIRK/Kir3 channels through increased protein stability of 14-3-3eta.
PG  - 298-310
LID - 10.1038/mp.2014.165 [doi]
AB  - A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces 
      a rapid antidepressant response. Lasting changes in the synapse structure and 
      composition underlie the effectiveness of these drugs. We recently discovered 
      that rapid antidepressants cause a shift in the gamma-aminobutyric acid receptor 
      (GABABR) signaling pathway, such that GABABR activation shifts from opening 
      inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting 
      dendritic calcium signal and mammalian Target of Rapamycin activity. However, 
      little is known about the molecular and biochemical mechanisms that initiate this 
      shift. Herein, we show that GABABR signaling to Kir3 (GIRK) channels decreases 
      with NMDAR blockade. Blocking NMDAR signaling stabilizes the adaptor protein 
      14-3-3eta, which decouples GABABR signaling from Kir3 and is required for the rapid 
      antidepressant efficacy. Consistent with these results, we find that key proteins 
      involved in GABABR signaling bidirectionally change in a depression model and 
      with rapid antidepressants. In socially defeated rodents, a model for depression, 
      GABABR and 14-3-3eta levels decrease in the hippocampus. The NMDAR antagonists AP5 
      and Ro-25-6981, acting as rapid antidepressants, increase GABABR and 14-3-3eta 
      expression and decrease Kir3.2. Taken together, these data suggest that the shift 
      in GABABR function requires a loss of GABABR-Kir3 channel activity mediated by 
      14-3-3eta. Our findings support a central role for 14-3-3eta in the efficacy of rapid 
      antidepressants and define a critical molecular mechanism for activity-dependent 
      alterations in GABABR signaling.
FAU - Workman, E R
AU  - Workman ER
AD  - 1] Center for Learning and Memory, Department of Neuroscience, Institute of 
      Neuroscience, University of Texas at Austin, Austin, TX, USA [2] Waggoner Center 
      for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, 
      USA.
FAU - Haddick, P C G
AU  - Haddick PC
AD  - Division of Research, Genentech, South San Francisco, CA, USA.
FAU - Bush, K
AU  - Bush K
AD  - Center for Learning and Memory, Department of Neuroscience, Institute of 
      Neuroscience, University of Texas at Austin, Austin, TX, USA.
FAU - Dilly, G A
AU  - Dilly GA
AD  - 1] Center for Learning and Memory, Department of Neuroscience, Institute of 
      Neuroscience, University of Texas at Austin, Austin, TX, USA [2] Institute for 
      Cell and Molecular Biology, University of Texas at Austin, Austin, TX, USA.
FAU - Niere, F
AU  - Niere F
AD  - 1] Center for Learning and Memory, Department of Neuroscience, Institute of 
      Neuroscience, University of Texas at Austin, Austin, TX, USA [2] Waggoner Center 
      for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, 
      USA.
FAU - Zemelman, B V
AU  - Zemelman BV
AD  - 1] Center for Learning and Memory, Department of Neuroscience, Institute of 
      Neuroscience, University of Texas at Austin, Austin, TX, USA [2] Institute for 
      Cell and Molecular Biology, University of Texas at Austin, Austin, TX, USA.
FAU - Raab-Graham, K F
AU  - Raab-Graham KF
AD  - 1] Center for Learning and Memory, Department of Neuroscience, Institute of 
      Neuroscience, University of Texas at Austin, Austin, TX, USA [2] Waggoner Center 
      for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX, 
      USA [3] Institute for Cell and Molecular Biology, University of Texas at Austin, 
      Austin, TX, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150106
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels)
RN  - 0 (Phenols)
RN  - 0 (Piperidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA-B)
RN  - 0 (Ro 25-6981)
RN  - 76326-31-3 (2-amino-5-phosphopentanoic acid)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - 14-3-3 Proteins/genetics/*metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Antidepressive Agents/*pharmacology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Excitatory Amino Acid Antagonists/pharmacology/therapeutic use
MH  - G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics/*metabolism
MH  - Immunoprecipitation
MH  - Male
MH  - Mice
MH  - Neurons/*drug effects
MH  - Phenols/pharmacology/therapeutic use
MH  - Piperidines/pharmacology/therapeutic use
MH  - Prefrontal Cortex/cytology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-B/genetics/*metabolism
MH  - Stress, Psychological/drug therapy/pathology/physiopathology
MH  - Swimming/psychology
MH  - Synaptosomes/drug effects/metabolism
MH  - Transduction, Genetic
MH  - Valine/analogs & derivatives/pharmacology/therapeutic use
PMC - PMC4357863
EDAT- 2015/01/07 06:00
MHDA- 2016/03/05 06:00
PMCR- 2015/03/13
CRDT- 2015/01/07 06:00
PHST- 2014/04/04 00:00 [received]
PHST- 2014/10/20 00:00 [revised]
PHST- 2014/10/22 00:00 [accepted]
PHST- 2015/01/07 06:00 [entrez]
PHST- 2015/01/07 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
PHST- 2015/03/13 00:00 [pmc-release]
AID - mp2014165 [pii]
AID - 10.1038/mp.2014.165 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2015 Mar;20(3):298-310. doi: 10.1038/mp.2014.165. Epub 2015 Jan 
      6.