| Objective To investigate the effect of various degrees of rapid eye movement(REM) sleep deprivation(SD),sleep revival and two GABAegic drugs(a selective GABA_AR antagonist SR-95531 and a selective GABA uptake blocker NO-711) intervention on cognitive performance of rats,GABA contents in rats' hypothalamus and expression of Fos and GABA_ARα1 subunit in Hypocretin neurons of rats' lateral hypothalamus,and to discuss possible relationship among REM SD, Hcrtergic system and GABAegic system in rats' hypothalamus.Methods Rats were divided into 3 groups randomly:cage control group(CC),tank control group(TG) and REM sleep deprivation group.REM sleep deprivation group was divided into non-operation control group(nonOP),Sham operation control group(Sham), SR-95531 administration group(SR) and NO-711 administration group(NO). Animals in REM sleep deprivation group were sacrificed at the end of 1d,3d,5d sleep deprivation periods respectively and at the end of 6h,12h sleep revival after 5d sleep deprivation.The modified multiple platform method(MMPM) was used to establish sleep deprivation model and the cognitive function was tested by Morris' maze. Immunofluorescence technique was used to analysis the counts of Hypocretin(Hcrt) immunoreaction neurons,total Fos immunoreaction cells,both Hcrt and Fos immunoreaction neurons,and GABA_ARα1 immunoreaction area integrated optical density(IOD) in rats' hypothalamus.High performance liquid chromatograph(HPLC) was specially used to analysis the quantitative level of GABA and glutamic acid (Glu)in rats' hypothalamus.Two GABAegic drugs,a selective GABA_AR antagonist SR-95531 and a selective blocker of type 1 GABA transporter(uptake blocker) NO-711,were used by perifomical nucleus microdialysis.Results There were no statistically significant differences(p＞0.05)in all tests of present research between CC and TC.As compared with CC and TC,cognitive function of nonOP and Shame was decreased by Morris' maze test(p＜0.05) in SD3d,SD5d and RS6h,while total Fos immunoreaction and Fos&Hcrt immunoreaction cells count and GABA_ARα1 immunoreaction area IOD were all increased by immunofluorescence technique test (p＜0.05),content of GABA was increased by HPLC(p＜0.05).There is a positive correlation between all these changes and the time suffered REM SD.As compared with CC and TC,cognitive function of NO was time-dependly decreased(p＜0.05) in SD1d,SD3d and SD5d,while content of GABA,total Fos and Fos&Hcrt cells count and GABA_ARα1 IOD were all time-dependly increased(p＜0.05).As compared with CC and TC,cognitive function of SR was decreased in RS6h and RS12h,while total Fos and Fos&Hcrt cells count and GABA_ARα1 IOD were all increased(p＜0.05).The content of GABA and GABA_ARα1 IOD of SR in SD1d,SD3d,SD5d,RS6h and RS12h were all higher than those of CC and TC(p＜0.05).While only GABA_ARα1 IOD of NO in SD5d was higher than that of CC and TC(p＜0.05).Conelusion REM SD not only time-dependly result in decrease of cognitive function of SD rats,but also time-dependly result in increase of GABA contents in rats' hypothalamus and expression of Fos and GABA_ARα1 subunit in Hypocretin neurons of rats' lateral hypothalamus.All these changes can recover after different degrees sleep revival. Among the course of REM SD and sleep revival,1) there is a self-regulating in GABAergic system of rat's hypothalamus,and this self-regulating mechanism has protective effect against sleep deprivation.2) there is a positive correlation between the activity of Hcrt ergic system and the force of GABAergic system,and they can co-regulate each other.Only on cognitive decreasion induced by REM SD, GABAergic system is not ideal therapeutic target for insomnia,but Hcrtergic system has more advantage to be a more potential one. |
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