Arousal effects of orexin A on acute alcohol intoxication-induced coma in rats

The key role of the hypothalamic neuropeptides orexins in maintenance and promotion of arousal has been well established in normal mammalian animals, but whether orexins exert arousal effects under pathological condition such as coma was little studied. In this study, a model of unconscious rats induced by acute alcohol intoxication was used to examine the effects of orexins through intracerebroventricular injection. The results revealed that either orexin A or orexin B induced decrease of duration of loss of right reflex in alcohol-induced unconscious rats. In the presence of the selective orexin receptor 1 antagonist SB 334867 and orexin receptor 2 antagonist TCS OX2 29, the excitatory action of orexin A was completely blocked. Our data further presented that orexin A also induced reduction of delta power in EEG in these rats. Single-unit recording experiment in vivo demonstrated that orexin A could evoke increase of firing activity of prefrontal cortex neurons in unconscious rats. This excitation was completely inhibited by an H(1) receptor antagonist, pyrilamine, whereas application of α(1)-adrenoreceptor antagonist prazosin or 5-HT(2) selective receptor antagonist ritanserin partially attenuated the excitatory effects of orexin A on these neurons. Consistently, the results of EEG recordings showed that microinjection of pyrilamine, prazosin, or ritanserin suppressed reduction of delta power in EEG induced by orexin A on unconscious rats. Thus, these data suggest that orexins exert arousal effects on alcohol-induced unconscious rats by the promotion of cortical activity through activation of histaminergic, noradrenergic and serotonergic systems. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.