睡眠剥夺快速抗抑郁机制中腺苷及其受体对CREB的影响
|
摘要
背景和目的:睡眠剥夺能够发挥快速抗抑郁效应,但其神经生物学机制至今尚不明确。睡眠剥夺过程中可观察到胞外腺苷水平明显升高及其受体发生一系列的变化,这提示腺苷系统在抑郁症病理生理、睡眠剥夺快速抗抑郁效应的机制、疗效等方面有一定作用。另一方面,CREB(环磷酸腺苷反应元件结合蛋白)是抑郁症相关信号通路中的一个交汇点。因此,本研究通过对慢性应激抑郁模型大鼠进行72小时快眼动睡眠剥夺并结合应用腺苷受体拮抗剂,观察海马和前皮质脑区CREB表达及磷酸化水平的变化,探讨腺苷在睡眠剥夺快速抗抑郁机制中可能的作用方式。
材料和方法:实验动物为成年雄性Sprague Dawley大鼠,随机分为正常对照组(n=9,以下称A组)、应激造模组(n=54)。应激造模组采用21天慢性轻度不可预见性应激(chronic mild unpredicted stress,CMUS)和分养两种经典模型结合的方式来建立抑郁模型,采用随机区组法把造模成功大鼠分为6组:抑郁模型组(B组)、睡眠剥夺组(C组)、水环境对照组(D组)、生理盐水对照组(E组)、腺苷A1受体拮抗剂组(F组)和腺苷A2a受体拮抗剂组(G组)、。利用小平台水环境法对抑郁模型大鼠进行快眼动睡眠剥夺,并用大平台水环境做对照,排除水环境的影响。采用自发活动测试和蔗糖水消耗实验观察大鼠抑郁行为的变化,Western-blot方法检测各组大鼠海马、前皮质CREB总蛋白及磷酸化水平的变化。
结果:
1.开场实验:大鼠经过21天CMUS后自发活动较正常对照组显著减少(P<0.01);C组大鼠经过72hREMSD后,自发活动与水环境对照组相比显著增加(P<0.01);F组大鼠经过72hREMSD后,自发活动无明显变化(P>0.05),与E组相比有显著差异(P<0.01);G组大鼠经过72hREMSD后,自发活动明显增加(P<0.01),而且与E组相比无统计学差异(P>0.05)。
2.蔗糖水消耗试验:大鼠经过21天CMUS处理后蔗糖水消耗量和蔗糖水消耗百分比均比正常对照组显著减少(P<0.01)。
3. CREB总蛋白(tCREB)及磷酸化水平(pCREB和pCREB/tCREB)的变化:
1)各处理方式对抑郁模型大鼠前皮质tCREB没有影响(P>0.05)。经过21天CMUS,大鼠前皮质磷酸化水平较正常对照组显著减少(P<0.01);72hREMSD使C、E组大鼠前皮质pCREB水平升高(P<0.01);F、G组大鼠前皮质pCREB水平明显低于与E组(P<0.01)。
2)各处理方式对抑郁模型大鼠海马tCREB没有影响(P>0.05)。经过21天CMUS,大鼠海马pCREB与正常对照组相比显著减少(P<0.01);72hREMSD使C、E组大鼠海马pCREB水平显著提高(P<0.05);F组大鼠前皮质pCREB水平显著低于生理盐水对照组(P<0.05);而G组在72hREMSD后大鼠海马pCREB明显高于B组(P<0.05),与E组相比差异没有统计学意义。
结论:
1. 21天CMUS可导致大鼠自发活动明显减少,72 h REMSD可快速逆转这种改变;在72 h REMSD过程中对大鼠注射腺苷A1受体拮抗剂可阻断REMSD在行为学上的效应,而在72 h REMSD过程中注射腺苷A2A受体拮抗剂,大鼠的自发活动仍可增加;
2. 21天CMUS降低大鼠海马和前皮质pCREB水平,可能是慢性应激导致大鼠抑郁样行为的机制之一;
3. 72hREMSD升高抑郁模型大鼠海马和前皮质pCREB水平,可能是REMSD抗抑郁效应的机制之一。
4.腺苷A1受体被拮抗时可阻断REMSD升高抑郁模型大鼠海马和前皮质pCREB水平的效应;腺苷A2A受体被拮抗时,REMSD仍可引起海马pCREB水平的升高,提示腺苷A1受体可能通过调节细胞内CREB相关信号通路参与REMSD的抗抑郁作用。
Backgrounds and objective:Sleep deprivation has a rapid antidepressant effect, but its neurobiological mechanisms is not clear so far. Now it is observed the levels of extracellular adenosine significantly increase and a series of changes of its receptors in the process of sleep deprivation,suggesting that the adenosine system play an important role in the pathophysiology of depression, rapid antidepressant effects of sleep deprivation.On the other hand, One protein that could serve as a convergence point for depression related multiple signaling pathways is the transcription factor CREB.Therefore,we studied the effects of 72 hour rapid-eye-movement sleep deprivation (REMSD) and adenosine A1 and A2A receptor antagonists on the CREB protein and phosphorylation level in hippocampus and prefrontal cortex of chronic mild unpredictable stress (CMUS) animal model to investigate the mechanisms of this antidepressant effects of sleep deprivation and the possible involvement of adenosine receptor.
Materials and methods:Adult male Sprague Dawley rats were divided into seven groups randomly:1) normal control group(group A);2)the depression-model group(group B);3) 72 hours sleep deprivation group(group C);4)72 hours tank control group(group D);5)adenosine A1 receptor antagonists group(group E);6)adenosine A2A receptor antagonists group(group F);7) saline group(group G). Two classical models were adopted to build depression-model, one is chronic mild unpredicted stresses, and the other is sub-raising. The REMSD group used a small platform water environment, in order to remove the influence of the water environment, a big platform was used as a control condition. Using spontaneous movements test and sucrose consumption test to observe the change of behavior in rats.Using Western-blot analysis to detect CREB and phosphorylation levels in hippocampus and frontal cortex.
Results:
1.Spontaneous movements;
Spontaneous movements decreased in the CMUS treated depressive animal model compare to the normal control rats. Spontaneous movements increased after 72h REMSD and treated with saline,adenosine A2A receptor antagonist.
2.sucrose consumption test;
The sucrose intake and the sucrose consumption percentage in the CMUS group were lower than those in the control group. The difference between the control and CMUS groups was significant.
3.CREB(tCREB) and phosphorylation levels(pCREB and pCREB/tCREB);
1)In frontal cortex,there were not significant diffrences of the levels of tCREB among the groups.The level of pCREB in group B was significantly lower than that in group A.Group C's pCREB level was significantly higher than that in group B.The level of pCREB in group E and F were no significant differences with group B,while the group G was significantly higher than group B.
2)In hippocampus,there were not significant differences of the levels of tCREB among the groups.The level of pCREB in group B was significantly lower than that in group A.Group C's pCREB level was significantly higher than that in group B.The group F and G were significantly higher than group B.
Conclusions:
1.CMUS can lead to depressive behavior in rats,and 72 h REMSD can quickly reverse of this change.Combind used with adenosine A1 receptor antagonist in the 72h REMSD process could inhibit the antidepressant effects the REMSD on behavior,however,injecting adenosine A2A receptor antagonist during 72h REMSD, the depression behavior can be still meliorated.
2.The level of pCREB in hippocampus and frontal cortex reduced after 21 days CMUS may be one of the mechanisms which lead to depression by chronic stress.
3.The level of pCREB in hippocampus and frontal cortex increased after 72 hours REMSD may be one of the mechanisms which lead to the antidepressant effect by REMSD.
4.In hippocampus,the effect that REMSD increased the level of pCREB may be inhibited when adenosine A1 receptor was antagonisted,but REMSD still increased pCREB level without A2A receptor activated.This indicated Adenosine A1 receptor involved in REMSD antidepressant effect through the regulation of intracellular CREB relevanted signaling pathways.
材料和方法:实验动物为成年雄性Sprague Dawley大鼠,随机分为正常对照组(n=9,以下称A组)、应激造模组(n=54)。应激造模组采用21天慢性轻度不可预见性应激(chronic mild unpredicted stress,CMUS)和分养两种经典模型结合的方式来建立抑郁模型,采用随机区组法把造模成功大鼠分为6组:抑郁模型组(B组)、睡眠剥夺组(C组)、水环境对照组(D组)、生理盐水对照组(E组)、腺苷A1受体拮抗剂组(F组)和腺苷A2a受体拮抗剂组(G组)、。利用小平台水环境法对抑郁模型大鼠进行快眼动睡眠剥夺,并用大平台水环境做对照,排除水环境的影响。采用自发活动测试和蔗糖水消耗实验观察大鼠抑郁行为的变化,Western-blot方法检测各组大鼠海马、前皮质CREB总蛋白及磷酸化水平的变化。
结果:
1.开场实验:大鼠经过21天CMUS后自发活动较正常对照组显著减少(P<0.01);C组大鼠经过72hREMSD后,自发活动与水环境对照组相比显著增加(P<0.01);F组大鼠经过72hREMSD后,自发活动无明显变化(P>0.05),与E组相比有显著差异(P<0.01);G组大鼠经过72hREMSD后,自发活动明显增加(P<0.01),而且与E组相比无统计学差异(P>0.05)。
2.蔗糖水消耗试验:大鼠经过21天CMUS处理后蔗糖水消耗量和蔗糖水消耗百分比均比正常对照组显著减少(P<0.01)。
3. CREB总蛋白(tCREB)及磷酸化水平(pCREB和pCREB/tCREB)的变化:
1)各处理方式对抑郁模型大鼠前皮质tCREB没有影响(P>0.05)。经过21天CMUS,大鼠前皮质磷酸化水平较正常对照组显著减少(P<0.01);72hREMSD使C、E组大鼠前皮质pCREB水平升高(P<0.01);F、G组大鼠前皮质pCREB水平明显低于与E组(P<0.01)。
2)各处理方式对抑郁模型大鼠海马tCREB没有影响(P>0.05)。经过21天CMUS,大鼠海马pCREB与正常对照组相比显著减少(P<0.01);72hREMSD使C、E组大鼠海马pCREB水平显著提高(P<0.05);F组大鼠前皮质pCREB水平显著低于生理盐水对照组(P<0.05);而G组在72hREMSD后大鼠海马pCREB明显高于B组(P<0.05),与E组相比差异没有统计学意义。
结论:
1. 21天CMUS可导致大鼠自发活动明显减少,72 h REMSD可快速逆转这种改变;在72 h REMSD过程中对大鼠注射腺苷A1受体拮抗剂可阻断REMSD在行为学上的效应,而在72 h REMSD过程中注射腺苷A2A受体拮抗剂,大鼠的自发活动仍可增加;
2. 21天CMUS降低大鼠海马和前皮质pCREB水平,可能是慢性应激导致大鼠抑郁样行为的机制之一;
3. 72hREMSD升高抑郁模型大鼠海马和前皮质pCREB水平,可能是REMSD抗抑郁效应的机制之一。
4.腺苷A1受体被拮抗时可阻断REMSD升高抑郁模型大鼠海马和前皮质pCREB水平的效应;腺苷A2A受体被拮抗时,REMSD仍可引起海马pCREB水平的升高,提示腺苷A1受体可能通过调节细胞内CREB相关信号通路参与REMSD的抗抑郁作用。
Backgrounds and objective:Sleep deprivation has a rapid antidepressant effect, but its neurobiological mechanisms is not clear so far. Now it is observed the levels of extracellular adenosine significantly increase and a series of changes of its receptors in the process of sleep deprivation,suggesting that the adenosine system play an important role in the pathophysiology of depression, rapid antidepressant effects of sleep deprivation.On the other hand, One protein that could serve as a convergence point for depression related multiple signaling pathways is the transcription factor CREB.Therefore,we studied the effects of 72 hour rapid-eye-movement sleep deprivation (REMSD) and adenosine A1 and A2A receptor antagonists on the CREB protein and phosphorylation level in hippocampus and prefrontal cortex of chronic mild unpredictable stress (CMUS) animal model to investigate the mechanisms of this antidepressant effects of sleep deprivation and the possible involvement of adenosine receptor.
Materials and methods:Adult male Sprague Dawley rats were divided into seven groups randomly:1) normal control group(group A);2)the depression-model group(group B);3) 72 hours sleep deprivation group(group C);4)72 hours tank control group(group D);5)adenosine A1 receptor antagonists group(group E);6)adenosine A2A receptor antagonists group(group F);7) saline group(group G). Two classical models were adopted to build depression-model, one is chronic mild unpredicted stresses, and the other is sub-raising. The REMSD group used a small platform water environment, in order to remove the influence of the water environment, a big platform was used as a control condition. Using spontaneous movements test and sucrose consumption test to observe the change of behavior in rats.Using Western-blot analysis to detect CREB and phosphorylation levels in hippocampus and frontal cortex.
Results:
1.Spontaneous movements;
Spontaneous movements decreased in the CMUS treated depressive animal model compare to the normal control rats. Spontaneous movements increased after 72h REMSD and treated with saline,adenosine A2A receptor antagonist.
2.sucrose consumption test;
The sucrose intake and the sucrose consumption percentage in the CMUS group were lower than those in the control group. The difference between the control and CMUS groups was significant.
3.CREB(tCREB) and phosphorylation levels(pCREB and pCREB/tCREB);
1)In frontal cortex,there were not significant diffrences of the levels of tCREB among the groups.The level of pCREB in group B was significantly lower than that in group A.Group C's pCREB level was significantly higher than that in group B.The level of pCREB in group E and F were no significant differences with group B,while the group G was significantly higher than group B.
2)In hippocampus,there were not significant differences of the levels of tCREB among the groups.The level of pCREB in group B was significantly lower than that in group A.Group C's pCREB level was significantly higher than that in group B.The group F and G were significantly higher than group B.
Conclusions:
1.CMUS can lead to depressive behavior in rats,and 72 h REMSD can quickly reverse of this change.Combind used with adenosine A1 receptor antagonist in the 72h REMSD process could inhibit the antidepressant effects the REMSD on behavior,however,injecting adenosine A2A receptor antagonist during 72h REMSD, the depression behavior can be still meliorated.
2.The level of pCREB in hippocampus and frontal cortex reduced after 21 days CMUS may be one of the mechanisms which lead to depression by chronic stress.
3.The level of pCREB in hippocampus and frontal cortex increased after 72 hours REMSD may be one of the mechanisms which lead to the antidepressant effect by REMSD.
4.In hippocampus,the effect that REMSD increased the level of pCREB may be inhibited when adenosine A1 receptor was antagonisted,but REMSD still increased pCREB level without A2A receptor activated.This indicated Adenosine A1 receptor involved in REMSD antidepressant effect through the regulation of intracellular CREB relevanted signaling pathways.
引文
[1].McKennaMT.Michaud CM.Murray CJ.et al.Assessing the burden of disease in the United States using disability-adjusted life years[J]. AmJ PrevMed,2005,28: 415.
[2].Nelson JC.A reviewof the ef?cacy of serotonergic and noradrenergic reuptake inhibitors for treatment of major depression. Biol Psychiatry,(1999)46:1301–1308.
[3].Baghai TC.Moller HJ.Rupprecht R.Recent Progress in pharmacological and non-pharmacological treatment options of major depression.Current Pharmaceutical Design,2006,12 (4):503-515.
[4].Henner G.Frank S.Therapeutic use of sleep deprivation in depression. Sleep Med Rev,2002,6(5):361-377.
[5].李慧.许崇涛.睡眠剥夺在抑郁症治疗中的研究进展.中国行为医学科学,2004,13 (1):10921101.
[6].Gillin JC.Buchsbaum MWJ.Clark C.Sleep deprivation as a model experimental anti-depressant treatment:findings from functional brain imaging.Depress Anxiety,2001,14(1):37-49.
[7].Elhwuegi AS.Central monoamines and their role in major depression.Prog Neuropsychopharmacol Biol Psychiatry.2004,28(3):435–451.
[8].Basheer R.Strecker RET.hakkar MM.et al.Adenosine and sleep-wake regulation.Prog Neurobiol,2004,73(6):379-396.
[9].Kaster MP.Rosa AO.Rosso MM. Adenosine administration produces an antidepressant- like effect in mice:evidence for the involvement of A1 and A2a receptors.Neurosci.Lett, 2004,355:21–24.
[10].Helmut L. Haas·Oliver Selbach. Functions of neuronal adenosine receptors. Naunyn-Schmiedeberg’s Arch Pharmacol,(2000) 362 :375–381.
[11].Porkka-Heiskanen,T.,Strecker,R.E.,Thakkar,M.,Bjorkum,A.A.,Greene,R.W.and McCarley R.W.Adenosine:a mediator of the sleep-inducing effects ofprolonged wakefulness.Science,(1997)276,1265–1268.
[12].Basheer,R.,Porkka-Heiskanen,T.,Strecker,R.E.,Thakkar,M.M.and McCarley,R.W. Adenosine as a biological signal mediating sleepiness following prolonged wakefulness,Biol.Signals Receptors,(2000)9, 319–327.
[13].Porkka-Heiskanen,T.,Strecker, R.E. and McCarley, R.W.Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep:an in vivo microdialysis study.Neuroscience,(2000)99,507–517.
[14].Rudolphi, K. A. and Schubert, P. 1997. Modulation of neuronal and glial cell function by adenosine and neuroprotection in vascular dementia. Behav. Brain Res,83:123–128.
[15].DiIorio,P.,Kleywegt,S.,Ciccarelli,R.,Traversa,U.,Andrew,C.M.,Crocker,C.E.,Werstiuk,E.S.,and Rathbone,M.P.Mechanisms of apoptosis induced by purine nucleosides in astrocytes.Glia, 2002,38:179–190.
[16].Coyle,J.T.and Duman,R.S.2003.Finding the intracellular signaling pathways affected by mood disorder treatments.Neuron,38(2):157–160.
[17].Elmenhorst D.Basheer R.McCarley RW.Bauer A.Sleep deprivation increases A1 adenosine receptor density in the rat brain.Brain Res,(2009)1258:53-8.
[18].Van Calker D and Biber K. The role of glial adenosine receptors in neural resilience and the neurobiology of mood disorders.Neurochem Res,(2005)30(10):1205–1217.
[19].Benington JH.Kodali SK. Heller HC.Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation. Brain Res,(1995)692:79–85.
[20].Wu J.Buchsbaum MS.Gillin JC.Tang C.Cadwell S.Wiegand M.Najafi A.Klein E.Hazen K.Bunney WE Jr.Fallon JH.Keator D.Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex. Am J Psychiatry,(1999) 156:1149–1158;erratum 156:1666.
[21].Julie A.Blendy.The Role of CREB in Depression and AntidepressantTreatment[J].B iol Psychiatry,2006,59:1144.
[22].Nibuya M.Morinobu S.Duman RS.Regulation of BDNF and trkB mRNA by chronic electroconvulsive seizure and antidepressant drug treatments.J Neurosci,(1995) 15:7539–7547.
[23].Manji HK.Quiroz JA.Sporn J,et al.Enhancing neuronal plasticity and cellular resilience to develop novel,improved therapeutics for difficult to treat depression.Biol.Psychiatry,2003.53:707-742.
[24].Laifenfeld D,Karry R,Grauer E,et al. Antidepressants and prolonged stress in ratsmodulate CAM-L1,laminin,and P-CREB,implicated in neuronal p lasticity[ J ]. NeurobiolDis,2005,20:432.
[25].Martin KC.Miehae D.RoseJC.BaradM.CadadioA.etal.MAP kinase translocate in to the nucleus of the Presynpatic cell and its required of long-term facilitationinAPlysia.Neuorn,1997,18:899-912.
[26].Haihong Li.Lei Zhang.Qingjun Huang.Differential expression of mitogen-activated protein kinase signaling pathway in the hippocampus of rats exposed to chronic unpredictable stress. Behavioural Brain Research, 205 (2009) 32–37.
[27].张晓斌.张志珺.谢春明.隋玉秀.孙奕.奚广军.氟西汀对抑郁模型大鼠海马区胶质细胞源性神经营养因子mRNA表达的影响.东南大学学报,2009年6月28卷3期。
[28].Pariante CM.Depression,stress and the adrenal axis.J Neuroendocrinol,2003,15(8):811-812.
[29].Nestler EJ.Gould E.Manji H.Preclinical models:status of basic research in depression.Biol Psychiatry,2002 Sep 15;52(6):503-528.
[30].Willnera P, Mitchellb P J, The validity of animal models of predisposition to depression, Behavioural Pharmacology.2002,13(3):169-188.
[31].李晓秋.许晶.抑郁动物模型的研究进展.中华精神科杂志,2002,35(3):184-186.
[32]. Giedke H.Frank Schwarzler.Therapeutic use of sleep deprivation in depression.Sleep Med Rev,2002,6:36123771.
[33].李慧,许崇涛.睡眠剥夺在抑郁症治疗中的研究进展.中国行为医学科学,2004 ,13 (1) :10921101.
[34].刘大志.朱兴族.腺苷在脑缺血过程中的双重作用.生命科学,2005,17(3):227-230.
[36].J.A.Ribeiro.,A.M.Sebasti?o,A.de Mendonca.Adenosine receptors in the nervous system:pathophysiological implications. Progress in Neurobiology,68 (2003) 377–392.
[37].张金玲.许崇涛.不同剂量腺苷对大鼠自发活动的影响.汕头大学医学院学报,2006,19(4)211-217.
[38]. Minor TR.WinslowJL.Chang WC.Stress and adenosine:II.Adenosine analogs mimic the effect of inescapable shock on shuttle escape per formance in rats[J ]. Behav Neurosci,1994,108:265-276.
[39].Thakkar MM.Winston S.McCarley RW.A1 receptor and adenosinergic homeostatic regulation of sleep-wakefulness:effects of antisebse to the A1 receptor in the cholinergic basal forebrain.J Neurosci,2003,23:4278-4287.
[40].Liu ZW.Gao XB.Adenosine inhibits activity of hypocretin/orexin neurons by the A1 receptor in the lateral hypothalamus:a possible sleep-promoting effect.J Neurophysiol,2007,97(1):837-848.
[41].Marks GA.Birabil CG.Speciale SG.Adenosine A1 receptors mediate inhibition of cAMP formation in vitro in the pontine,REM sleep induction zone.Brain Res,2001 Nov 9;1061(2):124-127.
[42].Tanase D.Baghdoyan HA.Lydic R.Dialysis delivery of an adenosine A1 receptor agonist to the pontine reticular formation decreases acetylcholine release and increases anesthesia recovery time.Anesthesiology,2003 Apr;98(4):912-920.
[43].Van Calker D and Biber K. The role of glial adenosine receptors in neural resilience and the neurobiology of mood disorders.Neurochem Res,2005,30(10):1205–1217.
[44].EI Yacoubi M.Ledent C.Parmentier M et al.Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice.Br.J.Pharmacol,2001,134(1):68-77.
[45].Malika E Y.Jean Costentin.Jean M V.Adenosine A2A receptors and depression.Neurology,2003,61(Suppl 6):S82–S87.
[46].Diaz-Cabiale.Z.,Hurd.Y.,Guidolin.D.,Finnman.U.-B.,Zoli.M.,Agnati.L.F., Vanderhaeghen.J.-J.,Fuxe,K.,Ferre,S.,Adenosine A2A agonist CG 21680decreases the affinity of dopamine D2 receptors for dopamine in human striatum. Neuroreport,2001,12,1831–1834.
[47].Rimondini.R.,Ferre,S.,Gimenez-Llort.L.,Ogren.S.O.,Fuxe.K., Differential effects of selective adenosine A1 and A2A receptor agonists on dopamine receptor agonist-induced behavioral responses in rats. Eur. J. Pharmacol,1998.347, 153–158.
[48].Benedetti F.Campori E.Barbini B.Dopaminergic augmentation of sleep deprivation effects in bipolar depression,Psychiatry research,2001,104(3):239-246.
[49].Petzer J P.Steyn S.Castagnoli K P.Inhibition of Monoamine Oxidase B by Selective Adeno- sine A2A Receptor Antagonists.Bioorganic &Medicinal Chemistry,2003,11(7):1299-1310.
[50].Drevets WC.Price JL.SimPson RJ , et al.Subgenual Prerfontal cortex abnormalities in mood disorders.Nature,1997,386:824-827.
[86].Rajkowska G.Postmoetem studies in mood disorders indicate altered numbers of neurons and glial cells.BiolPsychiatry,2000,48:766-777.
[51].Drevets WC.Functional anatomical abnormalities in limbic and prefrontal cortical sturctures in major depression.Prog Brain Res,2000,126:413-431.
[52].Janne Gr?nli.Clive Bramham.Robert Murison.Tambudzai Kanhema.Eldbj?rg Fiske.Bj?rn Bjorvatn.Reidun Ursin.Chiara M.Portas.Chronic mild stress inhibits BDNF protein expression and CREB activation in the dentate gyrus but not in the hippocampus proper. Pharmacology, Biochemistry and Behavior 85 (2006) 842–849.
[53].Lonze BE.Ginty DD.Function and regulation of CREB family transcription factors in the nervous system.Neuron,(2002):35:605–623.
[54].Bilang-Bleuel A.Rech J.De Carli S,et al. Forced swimming evokes a biphasic response in CREB phosphorylation in extrahypothalamic limbic and neocortical brain structures in the rat.Eur J Neurosci,2002;15 (6) : 1048-1060.
[55].Trentani A.Kuipers SD.Ter Horst GJ,et al.Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medialprefrontocortical dendrites:implications for stress-related cortical pathology ? Eur J Neurosci,2002;15(10):1681-1691.
[56]. Andres MK.Is major depression a neurologic dis order with psychiatric symptoms?Epilepsy &Behavior,2004;5(5):636-644.
[57]. Vinet J. Carra S.Blom JM,et al.Chronic treatment with desipramine and fluoxetine modulate BDNF, CaMKKalpha and CaMKKbeta mRNA levels in the hippocampus of transgenic mice expressing antisense RNA against the glucocorticoid receptor [J].Neuropharmacology,2004,47(7):1062
[58].D’Sa C.Duman R.Antidepressants and neuroplasticity.Bipolar Disord,2002,4:183.
[59].Thome J.Sakai N.Shin K,et al,cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment.J Neurosci,2000,20:4030-4036.
[60]. Chen AC.Shirayama Y.Shin KH,et al,Expression of the cAMP response element binding protein(CREB) in hippocampus produces an antidepressant effect.Biol Psychiatry,2001,49:753-762.
[61].Laurel.Graves.Allan pack.Ted Abel.Sleep and memory:a moecular perspective.Thends in Neurosciences,2001,24(4)237:243.
[62].Yasemin Gorgulu1.Okan Caliyurt.Rapid antidepressant effects of sleep deprivation therapy correlates with serum BDNF changes in major depression. Brain Research Bulletin,80(2009)158-162.
[63].张金玲.睡眠剥夺对正常大鼠和抑郁模型大鼠不同脑区腺苷A_1受体及5-HT_(1A)受体表达的影响[D].汕头大学,2007.
[64].Basheer R.Halldner L.Alanko L,et al,Opposite changes in adenosine A1 and A2A receptor mRNA following sleep deprivation.Neuroreport,2001a,12 :1577-1580.
[65].Elmenhorst D.Meyer PT.Winz OH,et al.Sleep deprivation increases A1 adenosine receptor binding in the human brain:a positron emission tomography study.J Neurosci,2007 Feb 28;27(9):2410-2415.
[66].Krystyna Go ? embiowska·Anna Dziubina.Involvement of adenosine in the effect of anti-depressants on glutamate and aspartate release in the rat prefrontal cortex.Naunyn- Schmiedeberg’s Arch Pharmacol,(2001)363:663–670.
[67].Alanko L.Urrila A.Stenberg D et al,Adenosine,energy metabolism,andsleep.Scientific World Journal,2003,20:790-798.
[68].de Mendonca.A.,Ribeiro.J.A., Adenosine and synaptic plasticity.Drug Dev.Res, 2001,52,283-290.
[69].Sebasti?o.A.M.,de Mendonca.A.,Moreira.T.,Ribeiro.J.A.,Activation of synaptic NMDA receptors by action potential-dependent release of transmitter during hypoxia impairs recovery of synaptic transmission on reoxygenation.J.Neurosci,2001b.21,8564-8571.
[70].Sun.M.K.,Xu.H.,Alkon.D.L.Pharmacological protection of synaptic function, spatial learning, and memory from transient hypoxia in rats.J.Pharmacol.Exp.Ther, 2002,300,408-416.
[71].de Mendonca.A.,Sebasti?o.A.M.,Ribeiro.J.A.,Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal neurons by adenosine A1 receptor activation.NeuroReport,1995,6,1097–1100.
[72].Hardingham.G.E.,Fukunaga.Y.,Bading.H.,Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways.Nat.Neurosci,2002.5,405-414.
[1]Basheer R,Strecker RE,Thakkar MM,et al. Adenosine and sleep-wake regulation.Prog Neurobiol,2004;73(6):379-396.
[2]Krystyna Go?embiowska·Anna Dziubina. Involvement of adenosine in the effect of anti-depressants on glutamate and aspartate release in the rat prefrontal cortex.Naunyn-Schmiedeberg’s Arch Pharmacol,2001;363:663–670.
[3]Kaster MP,Rosa AO,Rosso MM. Adenosine administration produces an antidepressant- like effect in mice:evidence for the involvement of A1 and A2a receptors.Neurosci.Lett, 2004,355:21–24.
[4]Porkka-Heiskanen T,Strecker RE,McCarley RW. Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study. Neuroscience,2000;99:507–517.
[5] Huang ZL,Urade Y,Hayaishi O. Prostaglandins and adenosine in the regulation of sleep and wakefulness.Current opinion in Pharmacol,2007;7:33-38.
[6]Urade Y,Eguchi N,Qu WM,et al. Sleep regulation in adenosine A2A receptor-de? cient mice. Neurology,2003;61:S94–S96.
[7]Hong ZY,Huang ZL,Qu WM,et al. An adenosine A2A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats. J. Neurochem,2005;92:1542–1549.
[8]Gallopin T,Luppi PH,Cauli B,et al. The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus. Neuroscience,2005;134:1377–1390.
[9]Oishi Y,Huang ZL,Fredholm BB,et al. Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1 receptors and promotes non-rapid eye movement sleep. Proc Natl Acad Sci U S A,2008;105(50):19992-7.
[10]Basheer R,Bauer A,Elmenhorst D,et al. Sleep deprivation upregulates A1 adenosine receptors in the rat basal forebrain. Neuroreport,2007;18:1895–1899.
[11]Elmenhorst D,Basheer R,McCarley RW,et al. Sleep deprivation increases A1 adenosine receptor density in the rat brain.Brain Res,2009;1258:53-8.
[12] Van Calker D and Biber K.The role of glial adenosine receptors in neural resilience and the neurobiology of mood disorders.Neurochem Res,2005;30(10):1205–1217.
[13]Lopes LV,Cunha RA,Kull B, et al. Adenosine A2A receptor facilitation of hippocampal synaptic transmission is dependent on tonic A1 receptor inhibition.Neuroscience,2002;112:319–329.
[14]Kaster MP,Santos AR,Rodrigues AL. Involvement of 5-HT1A receptors in the antidepressant-like effect of adenosine in the mouse forced swimming test.Brain Res Bull,2005;67(1-2):53-61.
[15]张金玲.睡眠剥夺对正常大鼠和抑郁模型大鼠不同脑区腺苷A_1受体及5-HT_(1A)受体表达的影响[D].汕头大学,2007.
[2].Nelson JC.A reviewof the ef?cacy of serotonergic and noradrenergic reuptake inhibitors for treatment of major depression. Biol Psychiatry,(1999)46:1301–1308.
[3].Baghai TC.Moller HJ.Rupprecht R.Recent Progress in pharmacological and non-pharmacological treatment options of major depression.Current Pharmaceutical Design,2006,12 (4):503-515.
[4].Henner G.Frank S.Therapeutic use of sleep deprivation in depression. Sleep Med Rev,2002,6(5):361-377.
[5].李慧.许崇涛.睡眠剥夺在抑郁症治疗中的研究进展.中国行为医学科学,2004,13 (1):10921101.
[6].Gillin JC.Buchsbaum MWJ.Clark C.Sleep deprivation as a model experimental anti-depressant treatment:findings from functional brain imaging.Depress Anxiety,2001,14(1):37-49.
[7].Elhwuegi AS.Central monoamines and their role in major depression.Prog Neuropsychopharmacol Biol Psychiatry.2004,28(3):435–451.
[8].Basheer R.Strecker RET.hakkar MM.et al.Adenosine and sleep-wake regulation.Prog Neurobiol,2004,73(6):379-396.
[9].Kaster MP.Rosa AO.Rosso MM. Adenosine administration produces an antidepressant- like effect in mice:evidence for the involvement of A1 and A2a receptors.Neurosci.Lett, 2004,355:21–24.
[10].Helmut L. Haas·Oliver Selbach. Functions of neuronal adenosine receptors. Naunyn-Schmiedeberg’s Arch Pharmacol,(2000) 362 :375–381.
[11].Porkka-Heiskanen,T.,Strecker,R.E.,Thakkar,M.,Bjorkum,A.A.,Greene,R.W.and McCarley R.W.Adenosine:a mediator of the sleep-inducing effects ofprolonged wakefulness.Science,(1997)276,1265–1268.
[12].Basheer,R.,Porkka-Heiskanen,T.,Strecker,R.E.,Thakkar,M.M.and McCarley,R.W. Adenosine as a biological signal mediating sleepiness following prolonged wakefulness,Biol.Signals Receptors,(2000)9, 319–327.
[13].Porkka-Heiskanen,T.,Strecker, R.E. and McCarley, R.W.Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep:an in vivo microdialysis study.Neuroscience,(2000)99,507–517.
[14].Rudolphi, K. A. and Schubert, P. 1997. Modulation of neuronal and glial cell function by adenosine and neuroprotection in vascular dementia. Behav. Brain Res,83:123–128.
[15].DiIorio,P.,Kleywegt,S.,Ciccarelli,R.,Traversa,U.,Andrew,C.M.,Crocker,C.E.,Werstiuk,E.S.,and Rathbone,M.P.Mechanisms of apoptosis induced by purine nucleosides in astrocytes.Glia, 2002,38:179–190.
[16].Coyle,J.T.and Duman,R.S.2003.Finding the intracellular signaling pathways affected by mood disorder treatments.Neuron,38(2):157–160.
[17].Elmenhorst D.Basheer R.McCarley RW.Bauer A.Sleep deprivation increases A1 adenosine receptor density in the rat brain.Brain Res,(2009)1258:53-8.
[18].Van Calker D and Biber K. The role of glial adenosine receptors in neural resilience and the neurobiology of mood disorders.Neurochem Res,(2005)30(10):1205–1217.
[19].Benington JH.Kodali SK. Heller HC.Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation. Brain Res,(1995)692:79–85.
[20].Wu J.Buchsbaum MS.Gillin JC.Tang C.Cadwell S.Wiegand M.Najafi A.Klein E.Hazen K.Bunney WE Jr.Fallon JH.Keator D.Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex. Am J Psychiatry,(1999) 156:1149–1158;erratum 156:1666.
[21].Julie A.Blendy.The Role of CREB in Depression and AntidepressantTreatment[J].B iol Psychiatry,2006,59:1144.
[22].Nibuya M.Morinobu S.Duman RS.Regulation of BDNF and trkB mRNA by chronic electroconvulsive seizure and antidepressant drug treatments.J Neurosci,(1995) 15:7539–7547.
[23].Manji HK.Quiroz JA.Sporn J,et al.Enhancing neuronal plasticity and cellular resilience to develop novel,improved therapeutics for difficult to treat depression.Biol.Psychiatry,2003.53:707-742.
[24].Laifenfeld D,Karry R,Grauer E,et al. Antidepressants and prolonged stress in ratsmodulate CAM-L1,laminin,and P-CREB,implicated in neuronal p lasticity[ J ]. NeurobiolDis,2005,20:432.
[25].Martin KC.Miehae D.RoseJC.BaradM.CadadioA.etal.MAP kinase translocate in to the nucleus of the Presynpatic cell and its required of long-term facilitationinAPlysia.Neuorn,1997,18:899-912.
[26].Haihong Li.Lei Zhang.Qingjun Huang.Differential expression of mitogen-activated protein kinase signaling pathway in the hippocampus of rats exposed to chronic unpredictable stress. Behavioural Brain Research, 205 (2009) 32–37.
[27].张晓斌.张志珺.谢春明.隋玉秀.孙奕.奚广军.氟西汀对抑郁模型大鼠海马区胶质细胞源性神经营养因子mRNA表达的影响.东南大学学报,2009年6月28卷3期。
[28].Pariante CM.Depression,stress and the adrenal axis.J Neuroendocrinol,2003,15(8):811-812.
[29].Nestler EJ.Gould E.Manji H.Preclinical models:status of basic research in depression.Biol Psychiatry,2002 Sep 15;52(6):503-528.
[30].Willnera P, Mitchellb P J, The validity of animal models of predisposition to depression, Behavioural Pharmacology.2002,13(3):169-188.
[31].李晓秋.许晶.抑郁动物模型的研究进展.中华精神科杂志,2002,35(3):184-186.
[32]. Giedke H.Frank Schwarzler.Therapeutic use of sleep deprivation in depression.Sleep Med Rev,2002,6:36123771.
[33].李慧,许崇涛.睡眠剥夺在抑郁症治疗中的研究进展.中国行为医学科学,2004 ,13 (1) :10921101.
[34].刘大志.朱兴族.腺苷在脑缺血过程中的双重作用.生命科学,2005,17(3):227-230.
[36].J.A.Ribeiro.,A.M.Sebasti?o,A.de Mendonca.Adenosine receptors in the nervous system:pathophysiological implications. Progress in Neurobiology,68 (2003) 377–392.
[37].张金玲.许崇涛.不同剂量腺苷对大鼠自发活动的影响.汕头大学医学院学报,2006,19(4)211-217.
[38]. Minor TR.WinslowJL.Chang WC.Stress and adenosine:II.Adenosine analogs mimic the effect of inescapable shock on shuttle escape per formance in rats[J ]. Behav Neurosci,1994,108:265-276.
[39].Thakkar MM.Winston S.McCarley RW.A1 receptor and adenosinergic homeostatic regulation of sleep-wakefulness:effects of antisebse to the A1 receptor in the cholinergic basal forebrain.J Neurosci,2003,23:4278-4287.
[40].Liu ZW.Gao XB.Adenosine inhibits activity of hypocretin/orexin neurons by the A1 receptor in the lateral hypothalamus:a possible sleep-promoting effect.J Neurophysiol,2007,97(1):837-848.
[41].Marks GA.Birabil CG.Speciale SG.Adenosine A1 receptors mediate inhibition of cAMP formation in vitro in the pontine,REM sleep induction zone.Brain Res,2001 Nov 9;1061(2):124-127.
[42].Tanase D.Baghdoyan HA.Lydic R.Dialysis delivery of an adenosine A1 receptor agonist to the pontine reticular formation decreases acetylcholine release and increases anesthesia recovery time.Anesthesiology,2003 Apr;98(4):912-920.
[43].Van Calker D and Biber K. The role of glial adenosine receptors in neural resilience and the neurobiology of mood disorders.Neurochem Res,2005,30(10):1205–1217.
[44].EI Yacoubi M.Ledent C.Parmentier M et al.Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice.Br.J.Pharmacol,2001,134(1):68-77.
[45].Malika E Y.Jean Costentin.Jean M V.Adenosine A2A receptors and depression.Neurology,2003,61(Suppl 6):S82–S87.
[46].Diaz-Cabiale.Z.,Hurd.Y.,Guidolin.D.,Finnman.U.-B.,Zoli.M.,Agnati.L.F., Vanderhaeghen.J.-J.,Fuxe,K.,Ferre,S.,Adenosine A2A agonist CG 21680decreases the affinity of dopamine D2 receptors for dopamine in human striatum. Neuroreport,2001,12,1831–1834.
[47].Rimondini.R.,Ferre,S.,Gimenez-Llort.L.,Ogren.S.O.,Fuxe.K., Differential effects of selective adenosine A1 and A2A receptor agonists on dopamine receptor agonist-induced behavioral responses in rats. Eur. J. Pharmacol,1998.347, 153–158.
[48].Benedetti F.Campori E.Barbini B.Dopaminergic augmentation of sleep deprivation effects in bipolar depression,Psychiatry research,2001,104(3):239-246.
[49].Petzer J P.Steyn S.Castagnoli K P.Inhibition of Monoamine Oxidase B by Selective Adeno- sine A2A Receptor Antagonists.Bioorganic &Medicinal Chemistry,2003,11(7):1299-1310.
[50].Drevets WC.Price JL.SimPson RJ , et al.Subgenual Prerfontal cortex abnormalities in mood disorders.Nature,1997,386:824-827.
[86].Rajkowska G.Postmoetem studies in mood disorders indicate altered numbers of neurons and glial cells.BiolPsychiatry,2000,48:766-777.
[51].Drevets WC.Functional anatomical abnormalities in limbic and prefrontal cortical sturctures in major depression.Prog Brain Res,2000,126:413-431.
[52].Janne Gr?nli.Clive Bramham.Robert Murison.Tambudzai Kanhema.Eldbj?rg Fiske.Bj?rn Bjorvatn.Reidun Ursin.Chiara M.Portas.Chronic mild stress inhibits BDNF protein expression and CREB activation in the dentate gyrus but not in the hippocampus proper. Pharmacology, Biochemistry and Behavior 85 (2006) 842–849.
[53].Lonze BE.Ginty DD.Function and regulation of CREB family transcription factors in the nervous system.Neuron,(2002):35:605–623.
[54].Bilang-Bleuel A.Rech J.De Carli S,et al. Forced swimming evokes a biphasic response in CREB phosphorylation in extrahypothalamic limbic and neocortical brain structures in the rat.Eur J Neurosci,2002;15 (6) : 1048-1060.
[55].Trentani A.Kuipers SD.Ter Horst GJ,et al.Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medialprefrontocortical dendrites:implications for stress-related cortical pathology ? Eur J Neurosci,2002;15(10):1681-1691.
[56]. Andres MK.Is major depression a neurologic dis order with psychiatric symptoms?Epilepsy &Behavior,2004;5(5):636-644.
[57]. Vinet J. Carra S.Blom JM,et al.Chronic treatment with desipramine and fluoxetine modulate BDNF, CaMKKalpha and CaMKKbeta mRNA levels in the hippocampus of transgenic mice expressing antisense RNA against the glucocorticoid receptor [J].Neuropharmacology,2004,47(7):1062
[58].D’Sa C.Duman R.Antidepressants and neuroplasticity.Bipolar Disord,2002,4:183.
[59].Thome J.Sakai N.Shin K,et al,cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment.J Neurosci,2000,20:4030-4036.
[60]. Chen AC.Shirayama Y.Shin KH,et al,Expression of the cAMP response element binding protein(CREB) in hippocampus produces an antidepressant effect.Biol Psychiatry,2001,49:753-762.
[61].Laurel.Graves.Allan pack.Ted Abel.Sleep and memory:a moecular perspective.Thends in Neurosciences,2001,24(4)237:243.
[62].Yasemin Gorgulu1.Okan Caliyurt.Rapid antidepressant effects of sleep deprivation therapy correlates with serum BDNF changes in major depression. Brain Research Bulletin,80(2009)158-162.
[63].张金玲.睡眠剥夺对正常大鼠和抑郁模型大鼠不同脑区腺苷A_1受体及5-HT_(1A)受体表达的影响[D].汕头大学,2007.
[64].Basheer R.Halldner L.Alanko L,et al,Opposite changes in adenosine A1 and A2A receptor mRNA following sleep deprivation.Neuroreport,2001a,12 :1577-1580.
[65].Elmenhorst D.Meyer PT.Winz OH,et al.Sleep deprivation increases A1 adenosine receptor binding in the human brain:a positron emission tomography study.J Neurosci,2007 Feb 28;27(9):2410-2415.
[66].Krystyna Go ? embiowska·Anna Dziubina.Involvement of adenosine in the effect of anti-depressants on glutamate and aspartate release in the rat prefrontal cortex.Naunyn- Schmiedeberg’s Arch Pharmacol,(2001)363:663–670.
[67].Alanko L.Urrila A.Stenberg D et al,Adenosine,energy metabolism,andsleep.Scientific World Journal,2003,20:790-798.
[68].de Mendonca.A.,Ribeiro.J.A., Adenosine and synaptic plasticity.Drug Dev.Res, 2001,52,283-290.
[69].Sebasti?o.A.M.,de Mendonca.A.,Moreira.T.,Ribeiro.J.A.,Activation of synaptic NMDA receptors by action potential-dependent release of transmitter during hypoxia impairs recovery of synaptic transmission on reoxygenation.J.Neurosci,2001b.21,8564-8571.
[70].Sun.M.K.,Xu.H.,Alkon.D.L.Pharmacological protection of synaptic function, spatial learning, and memory from transient hypoxia in rats.J.Pharmacol.Exp.Ther, 2002,300,408-416.
[71].de Mendonca.A.,Sebasti?o.A.M.,Ribeiro.J.A.,Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal neurons by adenosine A1 receptor activation.NeuroReport,1995,6,1097–1100.
[72].Hardingham.G.E.,Fukunaga.Y.,Bading.H.,Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways.Nat.Neurosci,2002.5,405-414.
[1]Basheer R,Strecker RE,Thakkar MM,et al. Adenosine and sleep-wake regulation.Prog Neurobiol,2004;73(6):379-396.
[2]Krystyna Go?embiowska·Anna Dziubina. Involvement of adenosine in the effect of anti-depressants on glutamate and aspartate release in the rat prefrontal cortex.Naunyn-Schmiedeberg’s Arch Pharmacol,2001;363:663–670.
[3]Kaster MP,Rosa AO,Rosso MM. Adenosine administration produces an antidepressant- like effect in mice:evidence for the involvement of A1 and A2a receptors.Neurosci.Lett, 2004,355:21–24.
[4]Porkka-Heiskanen T,Strecker RE,McCarley RW. Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study. Neuroscience,2000;99:507–517.
[5] Huang ZL,Urade Y,Hayaishi O. Prostaglandins and adenosine in the regulation of sleep and wakefulness.Current opinion in Pharmacol,2007;7:33-38.
[6]Urade Y,Eguchi N,Qu WM,et al. Sleep regulation in adenosine A2A receptor-de? cient mice. Neurology,2003;61:S94–S96.
[7]Hong ZY,Huang ZL,Qu WM,et al. An adenosine A2A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats. J. Neurochem,2005;92:1542–1549.
[8]Gallopin T,Luppi PH,Cauli B,et al. The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus. Neuroscience,2005;134:1377–1390.
[9]Oishi Y,Huang ZL,Fredholm BB,et al. Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1 receptors and promotes non-rapid eye movement sleep. Proc Natl Acad Sci U S A,2008;105(50):19992-7.
[10]Basheer R,Bauer A,Elmenhorst D,et al. Sleep deprivation upregulates A1 adenosine receptors in the rat basal forebrain. Neuroreport,2007;18:1895–1899.
[11]Elmenhorst D,Basheer R,McCarley RW,et al. Sleep deprivation increases A1 adenosine receptor density in the rat brain.Brain Res,2009;1258:53-8.
[12] Van Calker D and Biber K.The role of glial adenosine receptors in neural resilience and the neurobiology of mood disorders.Neurochem Res,2005;30(10):1205–1217.
[13]Lopes LV,Cunha RA,Kull B, et al. Adenosine A2A receptor facilitation of hippocampal synaptic transmission is dependent on tonic A1 receptor inhibition.Neuroscience,2002;112:319–329.
[14]Kaster MP,Santos AR,Rodrigues AL. Involvement of 5-HT1A receptors in the antidepressant-like effect of adenosine in the mouse forced swimming test.Brain Res Bull,2005;67(1-2):53-61.
[15]张金玲.睡眠剥夺对正常大鼠和抑郁模型大鼠不同脑区腺苷A_1受体及5-HT_(1A)受体表达的影响[D].汕头大学,2007.