Orexin A activates locus coeruleus cell firing and increases arousal in the rat

被引:976
作者
Hagan, JJ [1 ]
Leslie, RA [1 ]
Patel, S [1 ]
Evans, ML [1 ]
Wattam, TA [1 ]
Holmes, S [1 ]
Benham, CD [1 ]
Taylor, SG [1 ]
Routledge, C [1 ]
Hemmati, P [1 ]
Munton, RP [1 ]
Ashmeade, TE [1 ]
Shah, AS [1 ]
Hatcher, JP [1 ]
Hatcher, PD [1 ]
Jones, DNC [1 ]
Smith, MI [1 ]
Piper, DC [1 ]
Hunter, AJ [1 ]
Porter, RA [1 ]
Upton, N [1 ]
机构
[1] SmithKline Beecham Pharmaceut, Dept Discovery Chem, Harlow CM19 5AW, Essex, England
关键词
immunocytochemistry; hypothalamus; sleep; locomotor activity; grooming;
D O I
10.1073/pnas.96.19.10911
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The localization of orexin neuropeptides in the lateral hypothalamus has focused interest on their role in ingestion. The orexigenic neurones in the lateral hypothalamus, however, project widely in the brain, and thus the physiological role of orexins is likely to be complex. Here we describe an investigation of the action of orexin A in modulating the arousal state of rats by using a combination of tissue localization and electrophysiological and behavioral techniques. We show that the brain region receiving the densest innervation from orexinergic nerves is the locus coeruleus, a key modulator of attentional state, where application of orexin A increases cell firing of intrinsic noradrenergic neurones. Orexin A increases arousal and locomotor activity and modulates neuroendocrine function. The data suggest that orexin A plays an Important role in orchestrating the sleep-wake cycle.
引用
收藏
页码:10911 / 10916
页数:6
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