Effects of lateral preoptic area application of orexin-A on ... : NeuroReport (original) (raw)

SLEEP

Methippara, Melvi M1; Alam, Md Noor1,2; Szymusiak, Ronald2,3; McGinty, Dennis1,2,4

1Department of Psychology, University of California, Los Angeles, CA 90033, USA

2Veterans Affairs Greater Los Angeles Health Care System, 16111 Plummer Street, North Hills, CA 91343, USA

3Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90033, USA

4Corresponding Author: Dennis McGinty, Department of Psychology, University of California, Los Angeles, CA 90033, USA

Acknowledgements: This work was supported by the PHS grants (MH 47480 and HL 60296) and the Research Service of the Veterans Adiministration. Technical assistance provided by Ms Jing Wu is gratefully acknowledged.

Received 12 July 2000; accepted 18 August 2000

Abstract

Deficiency of orexin, a newly discovered hypothalamic peptide, is thought to lead to abnormal sleepiness and cataplexy in both human narcolepsy and animal models of the disease. As the POA contains extensive orexin terminals and is established as a sleep/arousal regulatory site, we evaluated a hypothesis that this site is a target for the arousal-inducing effects of orexin. Orexin-A was microinjected into lateral preoptic area (IPOA) and the effects on sleep–wakefulness and brain temperature were studied. Compared to saline vehicle control, orexin-A induced an increase in wakefulness for 70 min and suppressed all sleep stages, especially SWS2 and REM for 80 and 90 min, respectively. Brain temperature was not differentially affected by orexin-A compared to saline control. The orexin-induced arousal and REM suppression are consistent with the orexin-deficiency model of narcolepsy. Our results suggest that the IPOA orexin terminal field or adjacent structures may be a locus of arousal regulation by this peptide and a substrate of sleep-wake regulatory deficits in narcolepsy.