Getting on 'the GABA receptor shuttle' to treat anxiety disorders

October 22, 2009

Philadelphia, PA, 22 October 2009 - There are increasingly precise molecular insights into ways that stress exposure leads to fear and through which fear extinction resolves these fear states. Extinction is generally regarded as new inhibitory learning, but where the inhibition originates from remains to be determined. Gamma-aminobutyric acid (GABA), the primary inhibitory chemical messenger in the brain, seems to be very important to these processes.

A new article in Biological Psychiatry examined whether during the extinction of fear learning, GABA receptors may be inserted into the cell surface to reduce the excitability of the amygdala. Researchers inactivated a protein that links GABAA receptors to the cell surface. They found that this protein prevented fear extinction training and the local application of NMDA from increasing the number of GABAA receptors on the cell surface and enhancing the inhibition of amygdala nerve cells.

Lin and colleagues show that during fear conditioning, the number of GABAA receptors on the surface of neurons in the amygdala decreases, reducing the extent of inhibition of the neurons in this brain "fear center." When fear is extinguished by dissociating fear cues from unpleasant stimuli, the number of GABAA receptors on the cell surface of the amygdala neurons increases.

How does this happen? The study provides evidence of molecular mechanisms that shuttle GABAA receptors to the cell surface during extinction. The researchers showed that by inactivating a protein involved in the localization of GABAA receptors in the amygdala, they prevented the recruitment of GABA-mediated inhibition and extinction of fear. Dr. John Krystal, Editor of Biological Psychiatry comments: "This research provides evidence that we are starting to untangle the molecular mechanisms through which our cognitive and behavioral therapies might alter brain function."
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Notes to Editors:

The article is "Block of γ-Aminobutyric Acid-A Receptor Insertion in the Amygdala Impairs Extinction of Conditioned Fear" by Hui-Ching Lin, Sheng-Chun Mao, and Po-Wu Gean. The authors are affiliated with the Institute of Basic Medical Sciences and Department of Pharmacology, Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University, Tainan, Taiwan. The article appears in Biological Psychiatry, Volume 66, Issue 7 (October 1, 2009), published by Elsevier.

The authors' disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available at http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological_Psychiatry_Editorial_Disclosures_08_01_09.pdf.

Full text of the article mentioned above is available upon request. Contact Jayne M. Dawkins at ja.dawkins@elsevier.com to obtain a copy or to schedule an interview.

About Biological Psychiatry

This international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.

Biological Psychiatry (www.sobp.org/journal) is ranked 4th out of the 101 Psychiatry titles and 14th out of 219 Neurosciences titles on the 2008 ISI Journal Citations Reports® published by Thomson Scientific.

About Elsevier

Elsevier is a world-leading publisher of scientific, technical and medical information products and services. The company works in partnership with the global science and health communities to publish more than 2,000 journals, including the Lancet (www.thelancet.com) and Cell (www.cell.com), and close to 20,000 book titles, including major reference works from Mosby and Saunders. Elsevier's online solutions include ScienceDirect (www.sciencedirect.com), Scopus (www.scopus.com), Reaxys (www.reaxys.com), MD Consult (www.mdconsult.com) and Nursing Consult (www.nursingconsult.com), which enhance the productivity of science and health professionals, and the SciVal suite (www.scival.com) and MEDai's Pinpoint Review (www.medai.com), which help research and health care institutions deliver better outcomes more cost-effectively.

A global business headquartered in Amsterdam, Elsevier (www.elsevier.com) employs 7,000 people worldwide. The company is part of Reed Elsevier Group PLC (www.reedelsevier.com), a world-leading publisher and information provider. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

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