QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 29, 2009, 29(17):5381-5388; doi:10.1523/JNEUROSCI.0360-09.2009

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Coryell, M. W. Articles by Wemmie, J. A. Search for Related Content PubMed PubMed Citation Articles by Coryell, M. W. Articles by Wemmie, J. A.

 Previous Article  |  Next Article 

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

Matthew W. Coryell,¹ Amanda M. Wunsch,² Jill M. Haenfler,^2,6 Jason E. Allen,^2,6 Mikael Schnizler,⁴ Adam E. Ziemann,⁴ Melloni N. Cook,⁷ Jonathan P. Dunning,⁷ Margaret P. Price,⁵ Jon D. Rainier,⁸ Zhuqing Liu,⁸ Alan R. Light,^9,10 Douglas R. Langbehn,² and John A. Wemmie^1,2,3,6

¹Neuroscience Program, and Departments of ²Psychiatry, ³Neurosurgery, ⁴Physiology, and ⁵Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, and ⁶Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242, ⁷Psychology Department, The University of Memphis, Memphis, Tennessee 38152, and Departments of ⁸Chemistry, ⁹Anesthesiology, and ¹⁰Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah 84132

Correspondence should be addressed to Dr. John A. Wemmie, Department of Psychiatry, University of Iowa College of Medicine, 3139 Medical Laboratories, Iowa City, IA 52242. Email: john-wemmie{at}uiowa.edu

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.

---

Received Jan. 22, 2009; revised March 16, 2009; accepted March 23, 2009.

Correspondence should be addressed to Dr. John A. Wemmie, Department of Psychiatry, University of Iowa College of Medicine, 3139 Medical Laboratories, Iowa City, IA 52242. Email: john-wemmie{at}uiowa.edu

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2009 29: i. [Full Text]  

This article has been cited by other articles:

				Finally, a New Target for Antidepressants Journal Watch Psychiatry, May 22, 2009; 2009(522): 2 - 2. [Full Text]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help