Evidence map›Paper›PMID 25560757›Full record

ArticleMolecular psychiatry2015

Rapid antidepressants stimulate the decoupling of GABA(B) receptors from GIRK/Kir3 channels through increased protein stability of 14-3-3η.

E R Workman, P C G Haddick, K Bush, G A Dilly, F Niere, B V Zemelman, K F Raab-Graham

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
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  3. The involvement of KTranslational psychiatry · 2024
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  8. Frontiers in psychiatry · 2023
    Review
  9. Neuronal G protein-gated KAmerican journal of physiology. Cell physiology · 2022
    Review
  10. Mechanisms and Regulation of Neuronal GABACurrent topics in behavioral neurosciences · 2022
    Review
  11. Article
  12. Article
  13. Article
  14. Acute and subchronic PCP attenuate D2 autoreceptor signaling in substantia nigra dopamine neurons.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2019
    Article
  15. Review
  16. Article
  17. Review
  18. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

E R Workman1] 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.
P C G HaddickDivision of Research, Genentech, South San Francisco, CA, USA.
K BushCenter for Learning and Memory, Department of Neuroscience, Institute of Neuroscience, University of Texas at Austin, Austin, TX, USA.
G A Dilly1] 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.
F Niere1] 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.
B V Zemelman1] 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.
K F Raab-Graham1] 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.
The University of Texas at Austin · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 γ-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 14-3-3η, 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 14-3-3η levels decrease in the hippocampus. The NMDAR antagonists AP5 and Ro-25-6981, acting as rapid antidepressants, increase GABABR and 14-3-3η 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 14-3-3η. Our findings support a central role for 14-3-3η in the efficacy of rapid antidepressants and define a critical molecular mechanism for activity-dependent alterations in GABABR signaling.

Indexed as

14-3-3 ProteinsAnimalsAnimals, NewbornAntidepressive AgentsCells, CulturedDisease Models, AnimalExcitatory Amino Acid AntagonistsG Protein-Coupled Inwardly-Rectifying Potassium ChannelsImmunoprecipitationMaleMiceNeuronsPhenolsPiperidinesPrefrontal CortexRats14-3-3 Proteins2-amino-5-phosphopentanoic acidAntidepressive AgentsExcitatory Amino Acid AntagonistsG Protein-Coupled Inwardly-Rectifying Potassium ChannelsPhenolsPiperidinesReceptors, GABA-BRNA, MessengerRo 25-6981Valine

Identifiers

PMID25560757
PMCPMC4357863
OpenAlexW2066406363

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.