A key role for orexin in panic anxiety

Research output: Contribution to journalArticle

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A key role for orexin in panic anxiety. / 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.

In: Nature Medicine, Vol. 16, No. 1, 2010, p. 111-U149.

Research output: Contribution to journalArticle

Harvard

Johnson, PL, Truitt, W, Fitz, SD, Minick, PE, Dietrich, A, Sanghani, S, Träskman Bendz, L, Goddard, AW, Brundin, L & Shekhar, A 2010, 'A key role for orexin in panic anxiety', Nature Medicine, vol. 16, no. 1, pp. 111-U149. https://doi.org/10.1038/nm.2075

APA

Johnson, P. L., Truitt, W., Fitz, S. D., Minick, P. E., Dietrich, A., Sanghani, S., ... Shekhar, A. (2010). A key role for orexin in panic anxiety. Nature Medicine, 16(1), 111-U149. https://doi.org/10.1038/nm.2075

CBE

Johnson PL, Truitt W, Fitz SD, Minick PE, Dietrich A, Sanghani S, Träskman Bendz L, Goddard AW, Brundin L, Shekhar A. 2010. A key role for orexin in panic anxiety. Nature Medicine. 16(1):111-U149. https://doi.org/10.1038/nm.2075

MLA

Vancouver

Johnson PL, Truitt W, Fitz SD, Minick PE, Dietrich A, Sanghani S et al. A key role for orexin in panic anxiety. Nature Medicine. 2010;16(1):111-U149. https://doi.org/10.1038/nm.2075

Author

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. / A key role for orexin in panic anxiety. In: Nature Medicine. 2010 ; Vol. 16, No. 1. pp. 111-U149.

RIS

TY - JOUR

T1 - A key role for orexin in panic anxiety

AU - Johnson, Philip L.

AU - Truitt, William

AU - Fitz, Stephanie D.

AU - Minick, Pamela E.

AU - Dietrich, Amy

AU - Sanghani, Sonal

AU - Träskman Bendz, Lil

AU - Goddard, Andrew W.

AU - Brundin, Lena

AU - Shekhar, Anantha

PY - 2010

Y1 - 2010

N2 - Panic disorder is a severe anxiety disorder with recurrent, debilitating panic attacks. In individuals with panic disorder there is evidence of decreased central gamma-aminobutyric acid (GABA) activity as well as marked increases in autonomic and respiratory responses after intravenous infusions of hypertonic sodium lactate(1-3). 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(4-9). The dorsomedial-perifornical hypothalamus is enriched in neurons containing orexin (ORX, also known as hypocretin)(10), which have a crucial role in arousal(10,11), vigilance(10) and central autonomic mobilization(12), 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. (C) 2010 Nature America, Inc. All rights reserved.

AB - Panic disorder is a severe anxiety disorder with recurrent, debilitating panic attacks. In individuals with panic disorder there is evidence of decreased central gamma-aminobutyric acid (GABA) activity as well as marked increases in autonomic and respiratory responses after intravenous infusions of hypertonic sodium lactate(1-3). 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(4-9). The dorsomedial-perifornical hypothalamus is enriched in neurons containing orexin (ORX, also known as hypocretin)(10), which have a crucial role in arousal(10,11), vigilance(10) and central autonomic mobilization(12), 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. (C) 2010 Nature America, Inc. All rights reserved.

U2 - 10.1038/nm.2075

DO - 10.1038/nm.2075

M3 - Article

VL - 16

SP - 111-U149

JO - Nature Medicine

JF - Nature Medicine

SN - 1546-170X

IS - 1

ER -