Monoaminergic Mechanisms Of Orexin-A On Wake-promoting In Alcohol Coma Rat

For many years,the study of coma treatment have not get great progress because we know little about wake-promoting systym.As common in clinic,alcohol coma have no particular antidote,wake-promoting is the important part in the treatment of Alcohol coma.It has significant correlation between arousal system and coma.The knowlede of arousal system come into a new period because of discovery of the peptide orexin,orexin neurons are found only in the lateral hypothalamic area but project to the entire central nervous system,such as histaminergic neurons in the TMN,noradrenergic neurons in the LC,serotonergic neurons in the DR.If the mechanism of wake-promoting of orexin is correlated with monoaminergic neurotransmitter, jia xiao-jun has found orexin-A can decrease the coma time in early days,We study the mechanism of wake-promoting on alcohol coma of orexin-A on the rat by electrocorticogram.To found the mechanism of wake-promoting of orexin is correlated with monoaminergic neurotransmitter or not.一,Establishment experimental model1,Establishment of a rat model of alcohol coma2,Implant the EEGelectrode3,Implant the ventricular cannula二,Antagonist of monoaminergic neurotransmitter can prevented the excitatory effects of orexin-A or not.If it is right,These results indicate that the excitatory effects of orexin-A is mediated by activation of monoaminergic neurotransmitter.Blocking effect is monitored by ECoG,depth of coma is tell by the percent ofδwave in ECoG.Early test has indicate the percent ofδwave in ECoG can decrease by the excitatory effects of orexin-A.1,H₁ histamine antagonist pyrilamine prevented the excitatory effects of orexin-AThe percent ofδwave in ECoG was observed obviously increased after injection(icv) of pyrilamine,compare with control group.(p＜0.01);After injection(icv) of pyrilamine,we inject(icv) orexin-A,the percent ofδwave in ECoG was observed increased obviously compare with control group (p＜0.05);The percent ofδwave in ECoG was not decreased by the excitatory effects of orexin-A.These results indicate that the excitatory effects of orexin-A is block by pyrilamine obviously.2,α₁-adrenoreceptor antagonist prazosin prevented the excitatory effects of orexin-AThe percent ofδwave in ECoG was observed obviously increased after injection(icv) of prazosin,compare with control group.(p＜0.01);After injection(icv) of prazosin,we inject(icv) orexin-A,the percent ofδwave in ECoG was observed no obviously chang.(p＞0.05);The percent ofδwave in ECoG was not decreased by the excitatory effects of orexin-A.These results indicate that the excitatory effects of orexin-A is block by prazosin.3,5- serotonin selective receptor antagonist(5-HT₂) ritanserin prevented the excitatory effects of orexin-AThe percent ofδwave in ECoG was observed obviously increased after injection(icv) of ritanserin,compare with control group.(p＜0.01);After injection(icv) of ritanserin,we inject(icv) orexin-A,the percent ofδwave in ECoG was observed no obviously chang.(p＞0.05);The percent ofδwave in ECoG was not decreased by the excitatory effects of orexin-A.These results indicate that the excitatory effects of orexin-A is block by ritanserin.In summary,the excitatory effects of alcohol coma by orexin-A is mediated by activation of histaminergic,noradrenergic,serotonergic system.The effect of histaminergic neurotransmission is most important.These results indicate that the excitatory effects of orexin-A is mediated by activation of monoaminergic neurotransmitter.