Acid-Sensing Ion Channel-1a in the Amygdala, a Novel Therapeutic Target in Depression-Related Behavior

Matthew W Coryell; Amanda M Wunsch; Jill M Haenfler; Jason E Allen; Mikael Schnizler; Adam E Ziemann; Melloni N Cook; Jonathan P Dunning; Margaret P Price; Jon D Rainier; Zhuqing Liu; Alan R Light; Douglas R Langbehn; John A Wemmie

doi:10.1523/JNEUROSCI.0360-09.2009

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Acid-Sensing Ion Channel-1a in the Amygdala, a Novel Therapeutic Target in Depression-Related Behavior

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Acid-Sensing Ion Channel-1a in the Amygdala, a Novel Therapeutic Target in Depression-Related Behavior

Matthew W Coryell, Amanda M Wunsch, Jill M Haenfler, Jason E Allen, Mikael Schnizler, Adam E Ziemann, Melloni N Cook, Jonathan P Dunning, Margaret P Price, Jon D Rainier, …

The Journal of neuroscience, Vol.29(17), pp.5381-5388

04/29/2009

DOI: 10.1523/JNEUROSCI.0360-09.2009

PMCID: PMC2710967

PMID: 19403806

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Abstract

No animal models replicate the complexity of human depression. However, a number of behavioral tests in rodents are sensitive to antidepressants and may thus tap important underlying biological factors. Such models may also offer the best opportunity to discover novel treatments. Here, we used several of these models to test the hypothesis that the acid-sensing ion channel-1a (ASIC1a) might be targeted to reduce depression. Genetically disrupting ASIC1a in mice produced antidepressant-like effects in the forced swim test, the tail suspension test, and following unpredictable mild stress. Pharmacologically inhibiting ASIC1a also had antidepressant-like effects in the forced swim test. The effects of ASIC1a disruption in the forced swim test were independent of and additive to those of several commonly used antidepressants. Furthermore, ASIC1a disruption interfered with an important biochemical marker of depression, the ability of stress to reduce BDNF in the hippocampus. Restoring ASIC1a to the amygdala of ASIC1a −/− mice with a viral vector reversed the forced swim test effects, suggesting that the amygdala is a key site of ASIC1a action in depression-related behavior. These data are consistent with clinical studies emphasizing the importance of the amygdala in mood regulation, and suggest that ASIC1a antagonists may effectively combat depression.

Details

Title: Subtitle: Acid-Sensing Ion Channel-1a in the Amygdala, a Novel Therapeutic Target in Depression-Related Behavior
Creators: Matthew W Coryell - Neuroscience Program, and
Amanda M Wunsch - Psychiatry
Jill M Haenfler - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Jason E Allen - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Mikael Schnizler - Physiology, and
Adam E Ziemann - Physiology, and
Melloni N Cook - Psychology Department, The University of Memphis, Memphis, Tennessee 38152, and
Jonathan P Dunning - Psychology Department, The University of Memphis, Memphis, Tennessee 38152, and
Margaret P Price - Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, and
Jon D Rainier - Chemistry
Zhuqing Liu - Chemistry
Alan R Light - Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah 84132
Douglas R Langbehn - Psychiatry
John A Wemmie - Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.29(17), pp.5381-5388
DOI: 10.1523/JNEUROSCI.0360-09.2009
PMID: 19403806
PMCID: PMC2710967
NLM abbreviation: J Neurosci
ISSN: 0270-6474
eISSN: 1529-2401
Publisher: Society for Neuroscience
Language: English
Date published: 04/29/2009
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
Record Identifier: 9984004194102771

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