Effects Of Sleep Deprivation On Adenosine A₁ Receptor And 5-HT_1A Receptor In The Brain Of Normal Rats And Rats Treated With Chronic Stresses

Background: Adenosine is thought as a sleep factor, which modulates sleep viaits receptors. Adenosine A₁ receptor plays a key role in sleep process. Furthermore,adenosine also modulates some neurotransmitters release as a neuromodulator.Recently a few studies indicated that adenosine and its receptors related withdepression and antidepressant. It is known that sleep deprivation presents anantidepressant-like effect. However, the mechanism of the rapid antidepressanteffect of sleep deprivation has not been clarified. Although most of the studiesof sleep deprivation focus on monoamine system, there still is evidence indicatedthat adenosine system involved in sleep deprivation. Review all of the progressin this field, We hypotheses that adenosine system plays an important role inantidepressant mechanism of sleep deprivation. The questions remained are, Howadenosine levels change in different part of brain when receiving sleep deprivation,The relationship of adenosine levels with antidepressant effect, and which kindof adenosine receptors involved in the process. This study try to investigate themechanism of the antidepressant effects of sleep deprivation via adenosine passway in rats.Study One:Objective: To investigate the effect of SD on locamotor activities and expressionof adenosine A₁ receptor, 5-HT_1A receptor in corresponding brain. To analyze therelationship between adenosine A, receptor and antidepressant effect of SD.Materials and Methods: Male Sprague-Dawley rats were divided into threegroups randomly: 1) normal control rats, 2) sleep deprivation, 3) sleep deprivationcontrol. Locamotor activities were performed in the 0,3rd day of the experiment.Animals were sacrificed at the third day of the experiment, the expression levelof adenosine A₁ receptor and 5-HT_1A receptor mRNA were studied by reversetranscription polymerase chain reaction (RT-PCR). The vitality of hippocampusnerve was tested by Nissle's staining. Results: 1) Following 72-hour sleep deprivation, locamotor activities increasedin SD group(P＜0.05, compared with SD control). 2) Sleep deprivation decreased thelevel of adenosine A₁ receptor in the hippocampus and midbrain (P＜0.05). sleepdeprivation had no effect on the the level of adenosine Am receptor mRNA inprefrontal cortex, hypothalamus and striate(P＞0.05). 3) Sleep deprivationincreased the level of 5-HT_1A receptor in the hippocampus and in prefrontalcortex(P＜0.05). Sleep deprivation decreased the level of 5-HT_1A receptor inmidbrain(P＜0.05). Seep deprivation had no effect on the the level of 5-HT_1A receptormRNA in hypothalamus and striate(P＞0.05). 4) Nissle's staining indicate that Sleepdeprivation increased the vitality of nerves in hippocampus(P＜0.05).Study Two:Objective: To investigate the effects of an 72-hour REM (rapid eye movement) sleepdeprivation on chronic mild unpredictable stress (CMUS) animal model and theexpression of adenosine A₁ receptor and 5-HT_1A receptor in the brain in chronic mildunpredictable stress (CMUS) animal model and after sleep deprivation.Materials and Methods: Sprague-Dawley rats were divided into two groupsrandomly: 1) normal control rats, 2) CMUS depressant animal model. Then after 21dCMUS, the depressant animal model were divided into three groups randomly: 3) thedepressant animal model,4) 72-hours REM sleep deprivation, 5) tank controlrats, Spontaneous movements were performed in the 0, 21th, 24th day of theexperiment. Animals were sacrificed, the expression level of adenosine A, receptorand 5-HT_1A receptor mRNA were studied by reverse transcription polymerase chainreaction (RT-PCR). the expression level of adenosine A₁ recetor protein werestudied by immunohistochemistry.Results: 1) Locamotor activities significantly slowed down in the CMUS depressantanimal model, compared with normal control rats(P＜0.05). Following 72-hour sleepdeprivation, locamotor activities increased in REMSD group(P＜0.05). (done by ZhangYinnan) 2) Chronic mild unpredictable stress can increase the level of adenosineA₁ receptor(mRNA and protein) in the hippocampus(P＜0.05), Sleep deprivation decreased the level of adenosine A₁ receptor(mRNA and protein) in thehippocampus(P＜0.05). 3) Chronic mild unpredictable stress can decrease the levelof adenosine A, receptor mRNA in prefrontal cortex(P＜0.05), but Sleep deprivationcannot come back the level of adenosine A₁ receptor mRNA in prefrontalcortex(P＞0.05). 4) Chronic mild unpredictable stress had no effect on the levelof adenosine A, receptor mRNA in hypothalamus(P＞0.05), but Sleep deprivation canincrease the level of adenosine A₁ receptor mRNA in hypothalamus(P＜0.05). 5)Chronic mild unpredictable stress and sleep deprivation had no effect on the thelevel of adenosine A₁ receptor mRNA in midbrain(P＞0.05). 6) The changes of 5-HT_1Areceptor mRNA expression are in the appendix(Done and analysed by Zhang Yinnan).Conclusions: sleep deprivation has an rapid antidepressant effect for CMUSdepressant rats. The up regulation of the expression of adenosine A₁ receptor inhippocampus and the down regulation of the expression of adenosine A₁ receptor inprefrontal cortex may take part in the pathogenesis of depression. Down regulationof the expression of adenosine A₁ receptor in hippocampus by REM sleep deprivationmay participate in the antidepressant-like effect of sleep deprivation. The upregulation of the expression of adenosine A₁ receptor in hypothalamus may also havean important effect. There may be some relation between adenosine A₁ receptor and5-HT in this course.