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Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats

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Abstract

Rationale

Anatomical studies have shown that the paraventricular nucleus of the thalamus (PVT) innervates areas of the forebrain involved in the expression and regulation of emotional behaviors including fear and anxiety. In addition, the PVT is densely innervated by fibers containing orexin-A (OXA) and orexin-B (OXB), peptides that are well-known for their arousal effects on behavior.

Objectives

In this study, we investigate whether microinjections of orexin receptor agonists and antagonists in the PVT region alter expression of anxiety-like behaviors in the rat as measured in the elevated plus maze.

Results

We report that microinjections of OXA and OXB in the PVT region elicited anxiety-like response as indicated by a reduction in open arm time and entries. In addition, OXA and OXB produced changes in ethological measures indicative of an anxiety state. Central administrations of antagonists for corticotropin releasing factor (CRF) or the opioid kappa receptors attenuated the anxiogenic effects produced by microinjections of OXA in the PVT region. We also provide evidence that endogenously released orexins act at the PVT to produce anxiety by showing that microinjections of TCSOX229, an orexin-2 receptor antagonist, in the PVT region attenuated the anxiogenic effects produced by a previous exposure to footshock stress.

Conclusions

This study indicates that endogenously released orexins act on the PVT to regulate anxiety levels through mechanisms involving the brain kappa and CRF receptors.

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Acknowledgments

The study was supported by Canadian Institutes of Health Research (CIHR; MOP68909 to G.J.K.); the National Basic Research Program Grants and the Chinese Academy of Sciences Grant (2009CB522002, KSCXI-TW-R-68 to N.S.); the NSFC Grants and the Project for Young Scientists Fund, Institute of Psychology, CAS (30600184, 07CX081008 to Y.L.). We also acknowledge Keke Qi and Xinwen Dong for their assistance in the analysis of ethological behaviors in the EPM test. The experiments comply with the Regulations for the Administration of Affairs Concerning Experimental Animals (China, 1988).

Conflict of interest

The authors declare that except for income received from their primary employer, no financial support or compensation has been received from any individual or corporate entity over the time when this research has been conducted and manuscript prepared.

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Authors and Affiliations

  1. Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China

    Yonghui Li, Chuguang Wei, Huiying Wang & Nan Sui

  2. Department of Oral Biology, University of Manitoba, 780 Bannatyne Avenue, Winnipeg, MB, R3E 0W2, Canada

    Yonghui Li, Sa Li & Gilbert J. Kirouac

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  1. Yonghui Li
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  2. Sa Li
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  3. Chuguang Wei
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  4. Huiying Wang
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  6. Gilbert J. Kirouac
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Correspondence to Gilbert J. Kirouac.

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Li, Y., Li, S., Wei, C. et al. Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats. Psychopharmacology 212, 251–265 (2010). https://doi.org/10.1007/s00213-010-1948-y

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