冲突性心理应激所致大鼠睡眠障碍的中枢5-HT的机制研究
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摘要
目的:建立冲突性心理应激所致大鼠睡眠障碍的大鼠模型并阐明其中枢5-HT机制。
     方法:
     1.大鼠冲突性心理应激模型的复制
     采用Vogel`s饮水冲突模型的改良方法,复制大鼠冲突性心理应激模型,并对造模后大鼠体质量、血清皮质酮浓度、以及在旷场迷宫中的行为学参数进行测定,进而确定冲突性心理应激模型复制成功的标准。
     2.冲突性心理应激大鼠睡眠时相和睡眠节律的变化
     采用大鼠皮层脑电描记技术,通过对大鼠脑电(EEG)和肌电(EMG)的监测,来考察冲突性心理应激对大鼠睡眠时相和睡眠节律的影响。
     3.冲突性心理应激所致大鼠睡眠障碍的中枢5-HT机制
     3.1冲突性心理应激大鼠中枢不同脑区睡眠相关神经递质含量的变化
     运用酶联免疫吸附法对冲突性心理应激大鼠睡眠和应激相关脑区(下丘脑、杏仁核和中缝核)5-HT、色氨酸羟化酶(TPH)、5-羟吲哚乙酸(5-HIAA)的含量进行测定,并推算出5-HIAA/5-HT的比值。
     3.2腹腔注射五羟色胺酸(5-HTP)对冲突性心理应激大鼠睡眠时相的影响
     给大鼠腹腔注射5-HT合成的前体物质5-羟色氨酸(5-HTP),通过对大鼠EEG和EMG的监测,考察5-HTP对冲突性心理应激大鼠睡眠时相和睡眠节律的影响。
     3.3冲突性心理应激大鼠外周血清中色氨酸浓度的变化
     采用高效液相色谱法测定冲突性心理应激大鼠外周血中色氨酸的浓度。
     3.4腹腔注射舍曲林对冲突性心理应激大鼠睡眠结构的影响
     考察神经突触前膜5-HT回吸收的抑制剂舍曲林对冲突性心理应激大鼠睡眠时相和睡眠节律的影响。
     3.5冲突性心理应激大鼠杏仁核部位S1c6a4基因和Htr1a基因表达的变化
     应用定量PCR技术考察冲突性心理应激对大鼠杏仁核部位5-HT转运体编码基因(S1c6a4)和5-HT1A受体编码基因(Htr1a)表达的影响。
     结果:
     1.大鼠冲突性心理应激模型的复制
     与空白组相比,模型组大鼠造模7d后,血清中CORT浓度显著升高(P<0.05),体质量显著性减少(P<0.05),在旷场迷宫中穿格数、直立次数和理毛次数明显减少(P<0.05),而排便次数显著增加(P<0.05)。
     2.冲突性心理应激大鼠的睡眠时相和睡眠节律的变化
     与空白组相比,模型组大鼠睡眠的LS、SWS、REM以及睡眠总时间都有不同程度的减少(P<0.05),除REM外其他各期所占睡眠总时间的比例均有不同程度的变化(P<0.05),且每个睡眠时相持续时间明显缩短,睡眠时相间的切换十分频繁,睡眠趋于零散化。
     3.冲突性心理应激所致大鼠睡眠障碍的中枢5-HT机制
     3.1冲突性心理应激大鼠中枢不同脑区睡眠相关神经递质含量的变化
     造模后大鼠中缝核部位、杏仁核部位以及下丘脑区的5-HT浓度显著降低(P<0.05)。中缝核部位和杏仁核部位的TPH浓度显著降低(P<0.05),TPH在下丘脑部位虽然有下降的趋势,但是与空白组相比无显著性差异(P>0.05)。模型组大鼠杏仁核部位和下丘脑部位的5-HIAA浓度显著降低(P<0.05),中缝核部位虽然有下降的趋势,但是和空白组相比无显著性差异(P>0.05)。由5-HIAA/5-HT的比值可以看出,模型组大鼠中缝核部位5-HIAA/5-HT的比值显著降低(P<0.05),而杏仁核部位和下丘脑区5-HIAA/5-HT的比值虽然有下降的趋势,但是与空白组相比,无显著性差异(P>0.05)。
     3.2腹腔注射五羟色胺酸(5-HTP)对冲突性心理应激大鼠睡眠时相的影响
     相对于模型组,5-HTP组大鼠睡眠总时间、LS、SWS和REM睡眠持续时间均显著延长(P<0.05),5-HTP组大鼠LS所占的比例显著减小(P<0.05),而SWS所占的比例显著增加(P<0.05),REM所占的比例基本不变(P>0.05)。且5-HTP组大鼠各个睡眠单元持续时间显著地延长,各睡眠时相之间的切换次数也有所减少,睡眠相对连续、集中。
     3.3冲突性心理应激大鼠外周血清中色氨酸浓度的变化
     与空白组相比,冲突性心理应激大鼠血清中的色氨酸水平明显降低(P<0.05)
     3.4腹腔注射舍曲林对冲突性心理应激大鼠睡眠结构的影响
     与模型组相比,舍曲林组大鼠睡眠总时间、LS、SWS和REM睡眠持续时间均显著延长(P<0.05),LS所占的比例显著减小(P<0.05),而SWS所占的比例显著增加(P<0.05),REM所占的比例与模型组大鼠相比变化不明显(P>0.05),大鼠的各个睡眠单元持续时间显著延长,各睡眠时相之间的切换次数也有所减少,睡眠趋于相对连续、集中。
     3.5冲突性心理应激大鼠杏仁核部位S1c6a4基因和Htr1a基因表达的变化
     与空白组相比,冲突性心理应激模型大鼠杏仁核部位的S1c6a4基因的表达明显升高,而杏仁核部位的Htr1a基因的表达量则有所降低。
     结论:冲突性心理应激对大鼠睡眠时相和睡眠节律造成显著影响,其影响的作用机制与降低中枢部分脑区5-HT的浓度和5-HT能神经系统的兴奋性、减少中枢5-HT的合成,促进神经突触间隙5-HT的回吸收以及减少突触后膜5-HT1A受体有关。
Objective:
     To establish the model of conflictive psychological stress in rats and investigate the mechanism of5-HT in conflictive psychological stress on rats'sleep phrase and sleep rhythm.
     Methods:
     1. Established the model of conflictive psychological stress in rats.
     The improved Vogel drinking conflictive model was used to establish the model of conflictive psychological stress in rats. The changes of weight, concentration of corticosterone (CORT) in serum and ethological parameters of rats were monitored. Then, the successfully copied standard of the model was established.
     2. The effect of conflictive psychological stress on sleep phase and sleep rhythm of rats.
     The cortical electroencephalography was used to monitor EEG and EMG of rats after suffering one week conflictive psychological stress to investigate the effect on sleep phase and sleep rhythm of rats.
     3. The mechanism of5-HT in conflictive psychological stress on rats' sleep phrase and sleep rhythm.
     3.1The effect of conflictive psychological stress on neurotransmitters in CNS.
     The Elisa method was used to evaluate the concentration of5-HT, TPH and5-HIAA in hypothalamus, amygdale and raphe nuclei. Then,5-HIAA/5-HT was worked out.
     3.2The effect of5-HTP on sleep phase and sleep rhythm of rats suffering to conflictive psychological stress.
     EEG and EMG of rats were monitorered after the precursor of5-HT,5-HTP, was injected to investigate the effect of5-HTP on sleep phase and rhythm of conflictive psychological stress rats.
     3.3The effect of conflictive psychological stress on concentration of tryptophane(trp) in peripheral blood.
     The HPLC was used to evaluate the concentration of trp in peripheral blood
     3.4The effect of Sertraline on sleep phase and sleep rhythm of rats suffering to conflictive psychological stress.
     Sertraline was injected to evaluate the effect of inhibitor of5-HT resorption in presynaptic membrane on sleep phase and sleep rhythm.
     3.5The effect of conflictive psychological stress on the expression of Slc6a4and Htrla in amygdale.
     PCR was used to evaluate the expression of Slc6a4and Htrla in amygdala after suffering to conflictive psychological stress
     Results:
     1. Established the model of conflictive psychological stress in rats.
     Compared with vehicle, rats in the model group showed increased concentration of CORT(P<0.05) and decreased body weight(P<0.05). In the open-field maze, however, the rats in model group showed more number of times of defecation(P<0.05), they passed less grids(P<0.05), showed less erect standing with hindlimb(P<0.05) and grooming(P<0.05).
     2. The effect of conflictive psychological stress on sleep phase and sleep rhythm of rats.
     Compared with vehicle, rats in model group showed less LS, SWS, REM, and TS(P<0.05). The ratio of every sleep phase in TS changed significantly (P<0.05) except for REM. The duration of sleep phase in model group reduced and the number of awakening increased; sleep tended to be fragmentation.
     3. The mechanism of5-HT in conflictive psychological stress on rats' sleep phrase and sleep rhythm.
     3.1The effect of conflictive psychological stress on neurotransmitters in CNS.
     Rats in model group showed lower concentration of5-HT in hypothalamus, amygdale and raphe nuclei(P<0.05). The concentration of TPH decreased significantly in amygdale and raphe nuclei (P<0.05). Though the concentration of TPH showed the trend to decrease in hypothalamus, no significance in statistics was performed (P>0.05). The concentration of5-HIAA decreased significantly in amygdale and hypothalamus (P<0.05). Though the concentration of5-HIAA showed the trend to decrease in raphe nuclei, no significance in statistics was performed (P>0.05). The specific value of5-HIAA/5-HT decreased significantly in raphe nuclei (P<0.05) Though the specific value of5-HIAA/5-HT showed the trend to decrease in amygdale and hypothalamus, no significance in statistics was performed (P>0.05)
     3.2The effect of5-HTP on sleep phase and sleep rhythm of rats suffering to conflictive psychological stress.
     Compared with model group, rats in5-HTP group showed more LS, SWS, REM, and TS (P<0.05). The ratio of LS in TS decreased significantly (P<0.05), while the SWS increased significantly (P<0.05). But the ratio of REM in TS did not change (P>0.05). The duration of sleep phase in5-HTP group increased and the number of awakening reduced. Sleep of rats in5-HTP group tended to be continuous and concentrated.
     3.3The effect of conflictive psychological stress on concentration of tryptophane (trp) in peripheral blood.
     Compared with vehicle, the concentration of trp in peripheral blood of rats in model group decreased significantly (P<0.05)
     3.4The effect of Sertraline on sleep phase and sleep rhythm of rats suffering to conflictive psychological stress.
     Compared with model group, rats in sertraline group showed more LS, SWS, REM, and TS (P<0.05). The ratio of LS in TS decreased significantly (P<0.05), while the SWS increased significantly (P<0.05). But the ratio of REM in TS did not change (P>0.05). The duration of sleep phase in sertraline group increased and the number of awakening reduced. Sleep of rats in sertraline group tended to be continuous and concentrated.
     3.5The effect of conflictive psychological stress on the expression of Slc6a4and Htrla in amygdale.
     Compared with vehicle, the expression of Slc6a4in amygdale increased significantly of rats in model group while the expression of Htrla showed the trend to decrease.
     Conclusion:
     Conflictive psychological stress can affect sleep phase and sleep rhythm of rats. The mechanism involved that it can reduce the concentration of5-HT and the excitability of5-HT energetic nervous system in the brain, reduce the synthesis of5-HT in CNS, promote synaptic cleft of5-HT resorption and reduced5-HT1A receptor in postsynaptic membrane.
引文
1.陈文,任超,刘娇,等.玫瑰花茶对束缚应激小鼠旷场活动性的影响.食品工业科技.2011,32(9):396-398.
    2.程义勇.心理应激研究进展..医药卫生技术进展.北京:军事医学科学出版社.1997:14-19.
    3.张乔.四逆散的有效组分改善睡眠作用的5-HT机制研究.黑龙江中医药大学,2012.
    4.李艳,徐碧云,肖芳,等.加味逍遥散对心理应激性失眠患者睡眠的影响.中国中西医结合杂志,2009,29(3):208-211.
    5.卢庆萍,张宏福.动物应激的研究进展.动物营养学报,2007,(S1):465-468
    6.蔡翘.selye应激学说与生理应激.生理科学进展,1963,(5):1-10
    7.韦有华,汤盛钦.几种主要的应激理论模型及其评价.心理科学,1998,(05):441-444
    8. Sheldon Cohen. Measuring stress:guide for Health and social scientists. Oxford University press,1995,8
    9.伍麟,车文博,郭增花.应激的多视角解析.健康心理学杂志,2004,(01):49-51
    10.孙莉,韩耀辉.心理应激研究与医学模式的发展.大连大学学报,1997,(04):125-129
    11. van de Kar LD, Blair ML. Forebrain pathways mediating stress-induced hormone secretion. Front Neuroendocrinol.1999,20(1):1-48.
    12. Gold PW, Chrousos GP. The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. Proc Assoc Am Physicians. 1999,111(1):22-34.
    13. Pacak K, Palkovits M. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocrine Rev.2001,22(4):502-548.
    14. Palkovits M. Interconnections between the neuroendocrine hypothalamus and the autonomic system. Front Neuroendocrinol.1999,20(4):270-295.
    15. Toth ZE, Gallatz K, Fodor M, et al. Decussations of the descending paraventricular pathways to the brainstem and spinal cord autonomic centers. J Comp Neurol.1999, 414(2):255-266.
    16. Spike RC, Puskar Z, Sakamoto H, et al. MOR-1-immunoreactive neurons in the dorsal horn of the rat spinal cord:evidence for nonsynaptic innervation by substance P-containing primary afferents and for selective activation by noxious thermal stimuli. Eur J Neurosci.2002,15(8):1306-1316.
    17. Potts JT, Lee SM, Anguelov PI. Tracing of projection neurons from the cervical dorsal horn to the medulla with the anterograde tracer biotinylated dextran amine. Auton Neurosci.2002,98(1-2):64-69.
    18.王宗文,严进,王云霞,等.几种不同应激源激活的特异性神经通路.中国行为医学科学.2005,14(8):766-768.
    19.画伟.心理应激胃粘膜损伤的动物模型及发病机制.国外医学消化系疾病分册.2002,22(3):143-145.
    20.朱国庆,钟明奎,张景行等.5-羟色胺和环磷酸腺苷对睡眠的影响.中国药理学通报,1999:14(2):141-143.
    21.赵乐章,章功良,高隽,等.中缝背核5-羟色胺能神经元在睡眠调节中的作用研究.中国应用生理学杂志,2003;19(2):175-178.
    22.章功良,何延龙,王烈成,等.腹外侧视前区5-羟色胺对大鼠睡眠-觉醒周期的作用.中国药理学通报,2003;19(8):931-934.
    23. Portas CM, etal:Brain Res.1994:648:306-312.
    24. Imeri L, etal. Neuroscience,1994:58:353-358
    25. Asikainen M, et al. NeuroReport,1997;8:1577-1582
    26.茅江峰,付勇,陆召麟.皮质醇增多症和精神异常.中华内分泌代谢杂志,2005;21(3):248-250.
    27. Born-J, etc.Hypothalamus-pituitary activity during human sleep:a coordinating role for the limbic hippocamal system. Exp clin endocrinol Diabetes.1998, 106(3):153-163.
    28.万秀琨,李铀,李亚琴等.银屑病患者血浆中β-内啡肤与睡眠质量的相关性研究.医学文选,2006:25(3):356-358.
    29. Dinesh Pal etal. Acta Physiologica Sinica,2005:57(4):401-403,
    30.徐莉萍,谢永标,刘破资等。原发性失眠患者血浆5-羟色胺和去甲肾上腺素与心理状况的相关分析.中国行为医学科学,2006;15(3):240-241.
    31.张瑾,李春华,钟明奎.海马CAI区微量注射去甲肾上腺素对慢波睡眠的影响.安徽医科 大学学报,2006:41(1):7-9.
    32.王志,林殷利.腹侧被盖区DA神经元调节睡眠-觉醒机制的探讨.生理学报,1997:04.49(2):135-140.
    33.张文慧,钱朝霞,汪海宏.大鼠中脑腹侧被盖区在睡眠-觉醒调节中的作用.生理学报,1995:47(2):195-200.
    34. Caldwell JL, etal. J Sleep Res.1997:6:92-101.
    35.李凌江,李则宣.精神应激的生物学致病机制(Ⅱ):神经内分泌机制.中国行为医学科学,2005,14:156-158.
    36.李艳,严灿,史亚飞等.反复心理应激大鼠血浆和下丘脑单胺神经递质的变化及加味四逆散的影响.中药药理与临床,2002;18(1):1-3
    37. Gaillard RC. Interaction between the hypothalamus-pituitary-adrenal axis and the immunological system. Ann Endocrinol,2001,62:155-163.
    38. Besedovsky HO, Rey A, Klusman I, et al. Cytokines as modulators of the hypothalamus-pituitary-adrenal axis. J Steroid Biochem Mol Biol,1991,40: 613-618.
    39. Ziad Kronfol, Daniel G. Cytokines and the Brain:Implications for clinical psychiatry. Am J Psychiatry.2000,157:683-694.
    40. Zorrilla EP, Luborsky L, McKay JR, et al. The relationship of depression and stressors to immunological assays:a meta-analytic review. Brain Behav Immun,2001, 15:199-226.
    41. Emily R, morey-Holton, Ruth K. Globus. Hind limb unloading rodent model:technical aspects. J Appl Physiol,2002,92(4):1367-1377
    42. B. J. Tucker, C. A. Mundy, M. G. Ziegler. Head-down tilt and restraint on renal function and glomerular dynamics in the rat. J App Physiol,1987,63:505-513
    43.曹碧茵,施建蓉,童瑶,邹军.心理应激动物模型的研制及其应用.中国行为医学科学,2005,(02):99-100
    44.郑丽芳,明亮.抑郁症动物模型的研究与应用.安徽医药,2005,(11):4-7
    45.王庆松,张建华.捕食应激对大鼠行为及空间学习记忆的影响.中华精神科杂志,2001,3:55-58.
    46.吴先哲.几种常用心理性胃粘膜损伤动物模型评述.湖北中医杂志,2002,24(3):52-53
    47.林文娟,王玮雯,邵枫.慢性情绪应激对大鼠行为、神经内分泌和免疫反应的影响:一个新的情绪应激模型.科学通报,2003,(09):926-929
    48.苏允爱,司天梅,舒良.精神分裂症动物模型研究进展.中国神经精神疾病杂志,2004,30(2):157-159
    49. JOHN R. HUGHES临床实用脑电图学.人民卫生出版社,1999:51-58
    50.张杰,王明时.睡眠脑电的研究.国外医学生物医学工程分册,1997,20(2):65-68
    51.寿天德神经生物学第一版高等教育出版社
    52. Edgar DM, Dement WC, Fuller CA. Effect of SCN lesions on sleep in squirrel monkeys:evidence for opponent processes in sleep-wake regulation. J Neurosci 1993:13:1065-1079. [PubMed:8441003]
    53. Jerome M. Siegel. (2005) Clues to the functions of mammalian sleep. Nature,437:1264-1271
    54. Sakurai T, Nagata R, Yamanaka A, et al. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron.2005,46(2):297-308.
    55. Achermann P and Borbely AA. Mathematical models of sleep regulation. Front Biosci. 2003,8:S683-S693.
    56. Dijk DJ and Czeisler CA. Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. J Neurosci.1995,15(5):3526-3538.
    57. Reppert SM and Weaver DR. Coordination of circadian timing in mammals. Nature. 2002,418:935-941.
    58. Jin X, Shearman LP, Weaver DR, et al. A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell.1999,96(1):1-20.
    59. McEwen BS and Stellar E. Stress and the individual. Mechanisms leading to disease. Arch Intern. Med.1993,153(18):2093-2101.
    60. Krout KE, Kawano J, Mettenleiter TC, et al. CNS inputs to the suprachiasmatic nucleus of the rat. Neuroscience.2002,110(1):73-92.
    61. Elmquist JK, Elias CF and Saper CB. From lesions to leptin:hypothalamic control of food intake and body weight. Neuron.1999,22,221-232.
    62. Elmquist JK, Ahima RS, Elias CF, et al. Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei. Proc. Natl Acad. Sci. USA.1998,95(2):741-746.
    63. Schachter SC and Saper CB. Vagus nerve stimulation. Epilepsia.1998,39(7):677-686.
    64. Yamanaka A, Beuckmann CT, Willie JT, et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron.2003,38(5):701-713.
    65.齐玉龙,翟长平.医学院校学生失眠症状及其相关因素探讨.蚌埤医学院学报2003,(01):77-78
    66.赵久波,张小远.军校医学生睡眠质量与心理应激水平的相关分析.南方医科大学学报.2006,26(6):792-793.
    67.张利萍,王培席,李彦芳.“5.12”两年后地震亲历者睡眠障碍与创伤后应激障碍的关联性探讨.中国实用护理杂志,2012,28(28):
    68.于鑫,李廷利.慢性心理应激对大鼠睡眠时相的影响.中医药学报.2012,40(6):22-24.
    69.桂丽.从睡眠时相和相关递质水平探讨加味逍遥散调治心理应激性失眠的机制.安徽医科大学,2007.
    70.徐瑞鑫,陈春苗,李廷利,等.冲突性心理应激对大鼠睡眠时相及睡眠节律的影响.中华行为医学与脑科学杂志,2012,29(2):208-211.
    71. Wurtamn RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res.1995,3(Suppl 4):477-480.
    72.高隽.中缝背核在深慢波睡眠调节中的作用研究.安徽医科大学.2001
    73. Dahlstrom A, Fuxe K. Evidence for the existence of monoanine neurons in the central nervous system I. Demonstration of monoanine in the cell bodies of brain stem neurons. Acta Phsiol Scand.1964,62(Suppl):232
    74.黄欢捷,邵蓓,何大楼,等.帕罗西汀对心理应激大鼠海马5-HT及c-fos表达的影响.医学研究杂志.2011,40(6):114-116.
    75.黄欢捷,邵蓓,何大楼,等.帕罗西汀对心理应激大鼠海马5-HT的影响.中国现代医生.2011,49(17):14-16.
    76.周建松,李凌江,曹霞,等.5-羟色胺及其突触后1A受体对慢性应激大鼠情绪和认知的 影响.中南大学学报(医学版),2008,33(4):305-311.
    77. Fuchs E, Czeh B, Kole M H, et al. Alterations of neuroplasticity in depression: the hippocampus and beyond. Eur Neuropsychopharmacol.2004,14 (5):S481-S490.
    78. Stockmeier CA, Shapiro LA, Dilley GE, et al. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci.1998,18 (18):7394-7401.
    79. Sargent PA, Kjaer KH, Bench CJ, et al. Brain serotoninlA receptor binding measured by positron emission tomography with [11C] WAY-100635:effects of depression and antidepressant treatment. Arch Gen Psychiatry.2000,57(2):174-180.
    80. Bhagwagar Z, Rabiner EA, Sargent PA, et al. Persistent reduction in brain serotoninlA receptor binding in recovered depressed men measured by positron emission tomography wih [11C] WAY-100635. Mol Psychiatry.2004,9(4):386-392.
    81.付乙.中药对运动性失眠单胺类神经递质和免疫功能的影响.四川中医,2004,22(4):13-15.
    82.神经精神药理学,库宝善主编,北京大学医学出版社2006年8月第一版,pp:96-98
    83.高振平,潘泽,孟祥辉,等.5-羟色胺细胞在成人脑干中缝核群的分布.白求恩医科大学学报,1998,24(1):35-36.
    84. Jouvet M. The role of monoamines and acetylcholine-containing neurons in the regulation of the sleep-waking cycle, Ergeb Physiol.,1972,64:166-307.
    85. Portas CM, McCarley RW, Behavioral state-related changes of extracellular serotonin concentration in the dorsal raphe nucleus:a microdialysis study in the freely moving cat, Brain Res.1994,648:306-312.
    86. Portas CM, Bjorvatn B, Fagerland S, et al, On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat, Neuroscience,1998,83:807-814.
    87. Houdouin F, Cespuqlio R, Jouvet M. Effect induced by the electrical stimulation of the nucleus raphe dorsalis upon hypothalamic release of 5-hydroxyindole compounds and sleep parameters in the rat, Brain Res.,1991,565:48-56.
    88.靳照宇,库宝善,姚海燕,等.5-HT1A和5-HT2受体功能与觉醒、睡眠成分关系的研究,中国药理学通报,2000,16(2):208-211.
    89. Monti JM, Jantos H, Silveira R, et al. Depletion of brain serotonin by 5,7-DHT: effects on the 8-OH-DPAT-induced changes of sleep and waking in the rat, Psychopharmacology (Berl),1994,115(1-2):273-277.
    90. Monti JM, Jantos H. Activation of the serotonin 5-HT3 receptor in the dorsal raphe nucleus suppresses REM sleep in the rat, Prog. Neuropsychopharmacol. Biol. Psychiatry,2008,32(4):940-947.
    91.黄莉莉,徐瑞鑫,卞宏生,等.基于5-HHT能神经系统的四逆散冻干粉改善睡眠的作用机制研究.哈尔滨医科大学学报.2011,45(3):214-217.
    92.李玉萍,徐瑞鑫,李廷利.四逆散冻干粉对睡眠剥夺果蝇头部5-HT含量和5-HTlA受体表达的影响.中国中药杂志.2010,35(20):2749-2751.
    93.黄俊山,曾雪爱,黄兆迁,等.松郁安神方对不同中医证型失眠患者血浆中5-羟色胺及多巴胺水平的影响.2011,52(24):2119-2120.
    94.高隽,朱国庆.5-羟色胺与睡眠和抑郁症的关系.国外医学精神病学分册.2000,27(3):148-152.
    95. Vogel JR, Beer B, Clody DE. A simple and rellable conflict procedure for testing anti-anxiety agents. Psychopharmacologia,1971,21:1-7.
    96.吴万振,陈夫银,张永东,等.冲突性应激致大鼠行为和内分泌的变化.中国行为医学科学.2005,14:391-393.
    97.李婷,朱婉儿,姜乾金.心理应激的生物学机制研究进展.中国行为医学科学,2005,14(9):862-864.
    98.王春生.针刺对不同应激源所致心理行为影响的实验研究.北京中医药大学,2008.
    99.朱玲勤,杨惠芳,张银娥,等.慢性心理应激对实验大鼠行为和免疫功能的影响.宁夏医学院学报,2007,29(4):376-378.
    100.田传胜,孙菲,王生.急性和重复性心理应激对大鼠血清皮质酮和免疫组织中糖皮质激素受体的影响.中国职业医学,2008,35:468-474.
    101. Bouyer JJ, Valle Me, Keminiere JM, et al. Reaction of sleep-wakefulnesscycle to stress is related to differences in hypothalamo-pituitary-adrenal axis reactivity in rat. Brain Research,1998,804:114-124.
    102.陈纯姿,于慧.两种不同慢性应激对大鼠体质量与自发活动的影响.汕头大学医学院学报,2009,22(4):218-220.
    103.胡冰,夏映红,袁海波,等.慢性可变应激对大鼠血压和行为学变化的影响.中国临床康复,2005,9(12):130-131.
    104.霍荣,王宝珍,李廷利.百麦安神冲剂对失眠大鼠睡眠时相的影响.中国医药导报.2008,25:16-18.
    105.姜姗姗,闫立地,李廷利,等.养心安神药与重镇安神药对失眠大鼠睡眠时相影响的比较研究.世界科学技术-中医药现代化.2010,12:405-408.
    106. Depoortere H. Some aspects of the polygraphic studies on sleep-wake-fulness cycle in rat. Waking sleeping,1980,4:47-62.
    107.库宝善.慢波睡眠的药理学研究.北京医科大学学报.1999,31:204-208.
    108.张杰,王明时.睡眠脑电的研究.国外医学生物医学工程分册.1997,20:65-68.
    109.霍荣,王宝珍,李廷利.百麦安神冲剂对失眠大鼠睡眠时相的影响.中国医药导报,2008,25:16-18.
    110. Palacios GV, Marquez SR, Jaime HB, et al. Further definition of the dffect of corticosterone the sleep-wake pattern in the male rat. Pharmacol Biochem Behav, 2001,70:3305-310.
    111.韩要武.两种不同品系大鼠焦虑反应对睡眠的影响及其部分机制研究.安徽医科大学.2005.
    112.方剑乔,梁宜,汪存信,等.经皮穴位电刺激对力竭运动大鼠海马、中脑5-HT及代谢产物含量影响的机制.中国康复医学杂志,2009,24(3):193-196.
    113.廖卫平,陆雪芬.高效液相色谱法测定血中游离、结合色氨酸及5-羟色胺.色谱,1992,10(2):118-119.
    114.洪煜,张蕴琨.脑组织中5-HT及受体与运动的研究现状.南京体育学院学报(自然科学版).2008,7(3):102-107.
    115.喻东上.抑郁症和皮质醇.中国行为医学科学.2000,9(4):317-318.
    116.刘占东,王得新,张宁,等.慢性疲劳综合征患者血浆中色氨酸水平测定.首都医科大学学报.2008,29(4):483-486.
    117.袁天懿,徐晨,查显友,等.舍曲林联合利培酮治疗精神分裂症阴性症状的临床观察.当代医学.2008,140:147-148.
    118.刘治军赵明陈乃宏,等.4种临床常见选择性5-羟色胺再摄取抑制剂对5-羟色胺转运体的抑制作用比较.中国药学杂志,2008,15:1149-1152.
    119.李玉萍.以果蝇为模式生物的四逆散改善睡眠作用及作用机制研究.黑龙江中医药大学,2009.
    120.张乔.四逆散的有效组分改善睡眠作用的5-HT机制研究.黑龙江中医药大学,2012.
    121.李玉萍,徐瑞鑫,李廷利.四逆散冻干粉对睡眠剥夺果蝇头部5-HT含量和5-HTlA受体表达的影响.中国中药杂志.2010,35(19):34-37.
    122. CAI Dingfang, SHEN Ziyin. Thinking of study on neuroen-docrino-immunological network of integratedtraditional and western medicine[J]. Chinese Journal of Integrated Traditional and Western Medicine,1997,17(7):442-445.
    123. Zalcman S. Interleukin-2 potentiates novelty-and GBR12909-induced exploratory activity.Brain Research,2001;899(1-2):1-9.
    124. Barone FC, Arvin B, White RF, et al. Tumor Necrosis Factor-a:A Mediator of Focal Ischemic Brain Injury. Stroke,1997,28:1233-1236
    125.李正银,赵法,郭俊生,等.锌对热应激大鼠POMC衍生肽的影响.解放军预防医学杂志,1998,16(3):163
    126.郑宇.不同应激源与针灸介入对精神心理及NEI网络改变的调控作用.北京中医药大学.2007.
    127.徐碧云,李艳,欧碧阳,等.心理应激性失眠患者情绪特征及其与个性行为的相关性分析.中国康复理论与实践.2008,14(10):972-973.
    128.李艳,徐碧云,杨志敏,等.心理应激性失眠患者主客观睡眠特征分析.临床精神医学杂志.临床精神医学杂志.2008,18(6):370-372.
    129. Vogel JR, Beer B, Clody DE. A simple and rellable conflict procedure for testing anti-anxiety agents. Psychopharmacologia,1971,21:1-7.
    130.吴万振,陈夫银,张永东,等.冲突性应激致大鼠行为和内分泌的变化.中国行为医学科学.2005,14:391-393.
    131.刘增平.足底电击应激对大鼠空间参考记忆维持及海马神经元性一氧化氮合酶表达的影响.中国临床康复,2006,10(6):54-56.
    132.吴红海,侯艳宁.足底电击诱发吗啡CPP重现大鼠杏仁核谷氨酸和GABA水平的变化.中华麻醉学杂志,2006,26(11):1024-1027.
    133.吴红海,王娜,侯艳宁.应激诱发吗啡条件性位置偏爱重现大鼠下丘脑和血浆中神经甾体水平的变化.解放军药学学报,2006,22(2):84-87.
    134. File S E, Pellow S. The effect of triazolobenzodiazepines in two animal tests of anxiety and in the holeboard. Journal de Pharmacologie,1985,86(3):729-735.
    135.亓晓丽,林文娟.焦虑和抑郁动物模型的研究方法和策略.心理科学进展,2005,13(3):327-332.
    136.王天芳,陈易新,季绍良,等.慢性束缚致慢性疲劳动物模型的研制及其行为学观察.中国中医基础医学杂志,1999,5(5):25-29.
    137. Larsson F, Winblad B, Mohammed AH. Psychological stress and environmental adaptation in enriched vs. impoverished housedrats. Pharmacol Biochem Behav,2002, 73(1):193-207.
    138.陈伟强,程义勇,等.心理应激对大鼠旷场行为的影响及酪氨酸干预作用研究.中国应用生理学杂志,2009,25(1):125-128.
    139.赵久波,张小远.军校医学生睡眠质量与心理应激水平的相关分析.南方医科大学学报,2006,26(6):792-793.
    140. Checky S. The neuroendocrinology of depression and chronic stress. Biol Psychiatry,1996,52:597-17.
    141. Bremner JD. Does stress damage the brain? Biol Psychiatry.1999,45:797-805.
    142.赵忠新.临床睡眠障碍学.第二军医大学出版社.2003,98-139.
    143.李艳,徐碧云,肖芳,等.加味逍遥散对心理应激性失眠患者睡眠的影响.中国中西医结合杂志,2009,29(3):208-211.
    144.徐瑞鑫,陈春苗,李廷利,等.冲突性心理应激对大鼠睡眠时相及睡眠节律的影响.中华行为医学与脑科学杂志,2012,29(2):208-211.
    145.高振平,潘泽,孟祥辉,等.5-羟色胺细胞在成人脑干中缝核群的分布[J],白求恩医科大学学报,1998,24(1):35-36.
    146. McCarley RW, Greene RW, Rainnie DG, et al. Brainstem neuromodulation and REM sleep. Semin. Neurosci,1995,7(5):341-354.
    147. Driver HS, Flanigan MJ, Benley AJ, et al. The influence of ipsapirone, a 5-HT1A agonist, on sleep pattens of healthy subjects. Psychopharmacology.1995,117(2): 186-192.
    148. Gillin JC, Sohn JW, Stahl SM, et al. Ipsapirone, a 5-HT1A agonist, suppresses REM sleep equally in unmediated depressed patients and normal controls. Neuropsychopharmacology.1996,15:109-115.
    149. Seifritz E, Moore P, Trachsel L, et al. The 5-HT1A agonist ipsapirone enhances EEG Slow wave activity in human sleep and produces a power spectrum similar to 5-HT2 blockade. Neurosci Lett.1996,209(1):41-44.
    150. Luebke JI, Greene RW, Semba K, et al. Serotonin hyperpolarizes cholinergic low threshold burst neurons in the rat laterodorsal tegmental nuelei in vitro. Proc Natl Acad Sci USA,1992,89:743.
    151. Leonard CS, Llinas R. Serotonergic and cholinergic inhibition of mesopontine cholinergic neurons controlling REM sleep:an vitro electrephysioogical study. Neuroscience,1994,59:309.
    152. Steriade M. Basic mechanisms of sleep generation. Neurology.1992,42:9-17.
    153. Sanford LD, Ross RJ, Seggos AE, et al. Central administration of two 5-HT receptor agonists:effect on REM sleep initiation and PGO waves. Pharmac. Biochem. Behav, 1994,49:93-100.
    154. MontiJM, Jantos H, Silveira R et al. Sleep and waking in 5,7-DHT-lesioned or (-)-pindolol-pretreated rats after administration of buspirone, ipsapirone, or grpirone. Pharmac Biochem Behav.1995b,52:305-312.
    155.孟德欣,牟丽,黄民,等.下丘脑Hypocretin神经肽在大鼠缰核对睡眠-觉醒调节中的作用[J].吉林大学学报(医学版),2009,35(2):214-218.
    156. Leonard D. E., Serotonin receptors and their function in sleep, anxiety disorders nd depression, Psychother. Psychosom,1996,65:66-75.
    157.李慧,林凌云,张印南,等.抑郁模型大鼠脑内色氨酸及5-羟色胺的改变.中华精神科杂志.2006,39(4):233-235.
    158. Jouvet M, The role of monoamines and acetylcholine-containing neurons in the regulation of the sleep-waking cycle, Ergeb Physiol.,1972,64:166-307.
    159.黄莉莉,徐瑞鑫,卞宏生,等.基于5-HT能神经系统的四逆散冻干粉改善睡眠的作用机制研究.哈尔滨医科大学学报,2011,45(3):214-217.
    160.张乔,金阳,徐瑞鑫,等.四逆散有效组分改善睡眠作用与5-羟色胺能神经系统相关性的实验研究.中国医药导报,2012,9(14):29-30,34.
    161.袁天懿,徐晨,查显友,等.舍曲林联合利培酮治疗精神分裂症阴性症状的临床观察. 当代医学.2008,140:147-148.
    162. Angel M, Esnuad H, Grallma D. Pharmacological characterization of the cloned human 5-hydroxytryptamine transporter. Biochem Pharmacol,1996,51(9):1145-51
    163. Lesch KP, Gross J, Franzek E, et al. Primary structure of the serotonin transporter in unipolar depression and bipolar disorder.Biol Psychiatry,1995,37(4):215-23
    164. Chen JX, Pan H, Rothman TP, et al. Guinea pig 5-HT transporter:cloning, expression, distribution, and function in intestinal sensory reception. Am J Physiol:Gastrointest Liver Physiol,1998,275(3):433.
    165. Lesch KP, Bengel D, HeilsA, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science,1996, 274(5292):1527-1531.
    166.吴兴曲,杨来启,王晓峰,等.睡眠剥夺后大鼠大脑5-HT1A和5-HT2A受体的表达.中国行为医学科学.2002,11(4):364-365.
    167. Peroutka SJ.5-HT receptor:past, present and future. Trends Neurosci,1995, 18(2):68-69.
    168. Meneses A, Hong E. Effect of fluoxetine on learning and mem-ory involves multiple 5-HTsystems. Pharmacol Biochem Behav,1995,52(2):341-346.
    169. Nakamura K, Kurasawa M. Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam. Naunyn Schmiedebergs Arch Pharmacol,2000,361(5):521-528.
    170.王竹风,汪宝军,岳广欣,等.慢性应激对脑区海马和杏仁核神经元影响的研究.辽宁中医杂志,2009,36(12):2028-2031.
    171.肖冰.PTSD大鼠杏仁核神经元Ca2+信号通路及COX和Caspase9的研究.中国医科大学.2010.
    172.潘霄,刘佳佳,严进,等.应激状态下记忆与杏仁核关系.中国健康心理学杂志,2011,19(2):252-254.
    173.施蕾,赵乐章,钟明奎,等.杏仁核微量注射cAMP和ATP对大鼠睡眠和觉醒的影响.蚌埠医学院学报,1998,23(4):217-218.
    174.吴兴曲,杨来启,王晓峰,等.约束应激对大鼠5-HT1A和5-HT2A受体表达的影响.中国临床心理学杂志,2003,11(3):225-227.

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