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 accessAbstract
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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Cites
Diagnostic and Statistical Manual of Mental Disorders
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The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity
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The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness
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Promotion of sleep by targeting the orexin system in rats, dogs and humans
Brisbare-Roch, C., Dingemanse, J., Koberstein, R., Hoever, P., Aissaoui, H., Flores, S., Mueller, C., Nayler, O., van Gerven, J., de Haas, S. L., et al. (2007) · Nature Medicine · doi:10.1038/nm1544 · Cited by 573
Orexin (Hypocretin) Neurons Contain Dynorphin
Chou, T. C., Lee, C. E., Lu, J., Elmquist, J. K., Hara, J., Willie, J. T., Beuckmann, C. T., Chemelli, R. M., Sakurai, T., Yanagisawa, M., et al. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-19-j0003.2001 · Cited by 429
Defensive burying in rodents: ethology, neurobiology and psychopharmacology
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Attenuated defense response and low basal blood pressure in orexin knockout mice
Kayaba, Y., Nakamura, A., Kasuya, Y., Ohuchi, T., Yanagisawa, M., Komuro, I., Fukuda, Y., & Kuwaki, T. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00671.2002 · Cited by 337
Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects
Rupprecht, R., Rammes, G., Eser, D., Baghai, T. C., Schüle, C., Nothdurfter, C., Troxler, T., Gentsch, C., Kalkman, H. O., Chaperon, F., et al. (2009) · Science · doi:10.1126/science.1175055 · Cited by 328
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Self-citation
Cited by
Control of sleep and wakefulness
Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012) · Physiological Reviews · doi:10.1152/physrev.00032.2011 · Cited by 1,477
Sex differences in anxiety and emotional behavior
Donner, N. C., & Lowry, C. A. (2013) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-013-1271-7 · Cited by 379
Placing the paraventricular nucleus of the thalamus within the brain circuits that control behavior
Kirouac, G. J. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.08.005 · Cited by 357
Hubs and spokes of the lateral hypothalamus: cell types, circuits and behaviour
Bonnavion, P., Mickelsen, L. E., Fujita, A., de Lecea, L., & Jackson, A. C. (2016) · The Journal of Physiology · doi:10.1113/jp271946 · Cited by 271
Circadian and wakefulness-sleep modulation of cognition in humans
Wright, K. P., Lowry, C. A., & LeBourgeois, M. K. (2012) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2012.00050 · Cited by 209
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
- Published
- 2009-12-27
- Volume
- 16
- Issue
- 1
- Pages
- 111-115
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2049637545
- Cited by
- 414
- References
- 32
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- green
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