Hypocretin/orexin contributes to the expression of some but not all forms of stress and arousal.
Hypocretin/orexin has a well-established role in wakefulness and in the maintenance of arousal. Because stress is associated with arousal, it has been proposed that hypocretin is also involved in stress. However, it is not clear if this is true for all forms of stress. To clarify this issue, we compared four conditions combining high arousal with no or low stress (wakefulness and exploration) or high stress (contextual fear and restraint) in the rat. We looked at Fos expression in hypocretin neurons, hypocretin-1 levels in cerebrospinal fluid and cardiovascular and behavioural changes after pharmacological blockade with the dual hypocretin receptor antagonist, almorexant. Fos expression in hypocretin neurons was highest with wakefulness and exploration, also high with fear but not significant with restraint. Hypocretin-1 levels were consistent with this pattern, although the differences were not as marked. Hypocretin receptor blockade with almorexant reduced the pressor, tachycardic and locomotor responses of wakefulness and exploration as well as the pressor and sympathetic component of the tachycardic response of fear. In contrast, almorexant did not reduce the pressor and tachycardic responses of restraint and nor did it reduce the pressor, tachycardic and locomotor responses of another stressor, i.e. cold exposure. Thus, hypocretin is not involved in all forms of stress. Comparison of the different conditions suggests that, regardless of stress, hypocretin involvement occurs when the arousal associated with the response includes increased attention to environmental cues. When it does, hypocretin will at least contribute to the cardiovascular response. The findings are of clinical relevance to some forms of psychological stress.
Furlong
Teri M
TM
School of Medical Sciences, University of New South Wales, NSW 2052, Australia.
Vianna
Daniel M L
DM
Liu
Lu
L
Carrive
Pascal
P
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D000068797:Orexins; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000134:cerebrospinal fluid / Q000378:metabolism*; D013997:Time Factors
D000081:Acetamides; D047908:Intracellular Signaling Peptides and Proteins; D007546:Isoquinolines; D009479:Neuropeptides; D016761:Oncogene Proteins v-fos; D000068797:Orexins; C519150:almorexant