Orexin 2 receptor in the nucleus accumbens is critical for the modulation of acute stress-induced anxiety.

Psychoneuroendocrinology
Bin LiXiaochun Peng

Abstract

Orexin is a neuropeptide mainly synthesized in the lateral hypothalamus/perifornical area and has been traditionally implicated in feeding, sleep-wake cycles, and reward. Intriguingly, patients with anxiety have increased levels of orexin in the cerebrospinal fluid. Pharmacological or genetic manipulation of orexin receptors affects anxiety-like behaviors in rodents, suggesting an involvement of the orexin signaling in the regulation of anxiety. Yet, the neural substrates involved remain largely unknown. The nucleus accumbens (NAc) shell holds a key position in the modulation of anxiety-related behaviors. Therefore, in the present study, by using neuropharmacology, molecular approaches and behavioral tests in rats, the role of orexin/orexin receptors in the NAc shell on the anxiety-like behaviors was investigated. We found that microinjection of orexin-A into the NAc shell induced an anxiogenic-like effect. Quantitative real-time PCR and immunofluorescence showed that the orexin 2 receptor (OX2R) is expressed and distributed in the NAc shell neurons. Activation of OX2R mimicked the anxiogenic effect of orexin-A. Moreover, infusion of an OX2R antagonist had no effect on anxiety-like behaviors in normal rats, but reversed anxioge...Continue Reading

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