Elsevier

Neuroscience Research

Volume 57, Issue 3, March 2007, Pages 462-466
Neuroscience Research

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Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats

https://doi.org/10.1016/j.neures.2006.11.009Get rights and content

Abstract

Orexins, recognized for their diverse functions in sleep/wakefulness/arousal and appetite regulation, may play provocative roles in stress response. Although the PVN of the hypothalamus expresses an abundance of orexin-2 receptor (OX-2R), the involvement of OX-2R in regulating ACTH response to stress remains unclear. To address this, we examined effects of a selective antagonist to OX-2R (N-{(1S)-1-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]carbonyl}-2,2-dimethylpropyl)-N-{4-pyridinylmethyl}amine upon plasma ACTH concentrations after administration of orexin A and swimming stress. Increases in ACTH levels with orexin A or swimming stress were attenuated with prior administration of an OX-2R antagonist. These results suggest that swimming stress facilitates ACTH release, at least in part via activation of OX-2R.

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Acknowledgements

We thank Banyu Pharmaceutical Company (Japan) for providing orexin-2 receptor antagonist, OX2-RA; and Dr. T. Sakurai for providing an anti-orexin antibody. This work was supported in part by the 21st Century COE Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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