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Cited by 414

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

A key role for orexin in panic anxiety

Open access
Johnson, Philip L, Truitt, William, Fitz, Stephanie D, Minick, Pamela E, Dietrich, Amy, Sanghani, Sonal, Träskman-Bendz, Lil, Goddard, Andrew W, Brundin, Lena, Shekhar, Anantha·2010·Nature Medicine
DOI 10.1038/nm.2075
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Abstract

Panic disorder is a severe anxiety disorder with recurrent, debilitating panic attacks. In individuals with panic disorder there is evidence of decreased central γ-aminobutyric acid (GABA) activity as well as marked increases in autonomic and respiratory responses after intravenous infusions of hypertonic sodium lactate. In a rat model of panic disorder, chronic inhibition of GABA synthesis in the dorsomedial-perifornical hypothalamus of rats produces anxiety-like states and a similar vulnerability to sodium lactate–induced cardioexcitatory responses. The dorsomedial-perifornical hypothalamus is enriched in neurons containing orexin (ORX, also known as hypocretin), which have a crucial role in arousal, vigilance and central autonomic mobilization, all of which are key components of panic. Here we show that activation of ORX-synthesizing neurons is necessary for developing a panic-prone state in the rat panic model, and either silencing of the hypothalamic gene encoding ORX (Hcrt) with RNAi or systemic ORX-1 receptor antagonists blocks the panic responses. Moreover, we show that human subjects with panic anxiety have elevated levels of ORX in the cerebrospinal fluid compared to subjects without panic anxiety. Taken together, our results suggest that the ORX system may be involved in the pathophysiology of panic anxiety and that ORX antagonists constitute a potential new treatment strategy for panic disorder.

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Metadata

Authors
Johnson, P. L., Truitt, W., Fitz, S. D., Minick, P. E., Dietrich, A., Sanghani, S., Träskman-Bendz, L., Goddard, A. W., Brundin, L., & Shekhar, A.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2009-12-27
Volume
16
Issue
1
Pages
111-115
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.2075
OpenAlex
W2049637545
Cited by
414
References
32
FWCI
11.42
Type
journal article
Language
en
Open access
green

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