社会隔离及居住入侵法诱导大鼠愤怒郁怒情绪反应及其评价方法
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:制备愤怒郁怒情绪反应大鼠模型,研究模型评价指标;检测动物体内相关递质、激素水平变化,初步探讨愤怒郁怒产生机理及药物干预可能机制。
     方法:用社会隔离(Social Isolation Paradigm)加居住入侵法(Resident Intruder Test)诱导愤怒情绪反应大鼠模型,以攻击行为测试为主,辅以旷场实验和糖水偏好测试区分怒情绪的两种亚型(愤怒、郁怒),并随之考察造模方法稳定性,然后进行药物干预。造模结束后收集血清及分离额叶皮质、顶区皮质、海马、下丘脑四个脑区。以放免法和HPLC分别检测ACTH、Cor、T、NE、DA、5-HT、GABA含量。
     结果:⑴与正常对照组相比,造模后第2周攻击行为得分高组(HA)和攻击行为得分低组(LA)大鼠体质量均显著降低(P<0.001);HA组和LA组大鼠肾上腺系数也显著增加(P<0.01)。
     ⑵攻击行为测试中,在两个周的造模时间内,HA组大鼠较LA组大鼠混合攻击行为得分显著增多(P<0.001, P<0.001),潜伏期显著缩短(P<0.001, P<0.001);旷场实验中,HA组、LA组与正常对照组相比,实验得分显著增多(P<0.01),且HA组大鼠得分与LA组相比亦显著增加(P<0.05);HA组、LA组的糖水偏好系数比正常对照组显著降低(P<0.01),但HA组、LA组大鼠之间无差别。
     ⑶大鼠模型微观指标检测方面,大鼠血清Cor含量,愤模组较郁模组相比,显著下降(P<0.01);大鼠血清5-HT含量愤模组较郁模组显著上升(P<0.05);给药后,愤药组与愤模组大鼠相比,血清5-HT含量异常波动得到明显纠正(P<0.05),血清中DA和NE没有显著性差异。
     与正常对照组相比,愤模组大鼠下丘脑NE含量显著下降(P<0.001),郁模组大鼠顶区皮质、海马NE含量显著上升(P<0.001,P<0.001),而下丘脑NE含量则显著下降(P<0.001)。愤模组与郁模组相比,大鼠顶区皮质、额叶皮质、海马NE含量显著下降(P<0.01,P<0.01,P<0.01),而下丘脑NE含量显著上升(P<0.001),给药后愤药组大鼠额叶皮质NE含量异常变化得以纠正(P<0.05)。
     与正常对照组相比,愤模组额叶皮质、顶区皮质、海马DA含量显著下降(P<0.001,P<0.001,P<0.001),而下丘脑DA含量则显著上升(P<0.001),给药后下丘脑DA含量恢复至正常水平(P<0.001)。与正常对照组相比,郁模组额叶皮质DA含量显著降低(P<0.001),而下丘脑DA含量则显著上升(P<0.001),药物干预后,下丘脑DA含量恢复至正常水平(P<0.05)。愤模组与郁模组相比,大鼠顶区皮质、海马DA含量显著下降(P<0.001,P<0.001)。
     与正常对照组相比,愤模组大鼠下丘脑5-HT含量显著降低(P<0.001)。与正常对照组相比,郁模组大鼠额叶皮质5-HT含量显著上升(P<0.05),而下丘脑5-HT含量则显著下降(P<0.001),给药后下丘脑5-HT含量得到明显纠正(P<0.001)。愤模组与郁模组相比,大鼠下丘脑5-HT含量显著上升(P<0.05)。
     结论:利用社会隔离加居住入侵法可成功制备愤怒郁怒情绪反应大鼠模型。造模方法可靠,具有较好的可信度及可重复性;应用攻击行为测试可明确区分愤怒郁怒情绪反应。①大鼠愤怒情绪反应与下丘脑NE含量下降,额叶皮质、顶区皮质、海马DA、下丘脑5-HT含量显著下降,下丘脑DA含量显著上升有关。②大鼠郁怒情绪反应与大鼠顶区皮质、海马NE、下丘脑DA、额叶皮质5-HT含量显著上升,下丘脑5-HT、NE、额叶皮质DA含量下降有关。因此我们可推断干预药物经前平颗粒、经前舒颗粒可能通过纠正上述指标异常变化而发挥药理作用,作用关键部位是中枢不同脑区。
Objective: Our aims of this study are to introduce rat model and research evaluative method of anger-out/in emotional reaction, to investigate changes of neurotransmitter and hormone and to initially explore the mechanism of rat model as well as effect of medicine.
     Methods: Model rats with anger-out/in emotional reaction are induced by social isolation paradigm plus resident intruder stress, after that we distinguished the difference between angry-out and anger-in by aggressive behavior test, supplemented by open-field test and sugar preference test, subsequently examine the stability of the modeling method, and then intervened with Jingqianping (Jingqianshu) granule. After model establishment,we killed the rats by decapitation,collected serum and dissected different brain regions(prefrontal cortex, parietal cortex, hippocampus and hypothalamus), detected ACTH, Cor, T,NE,DA,5-HT and GABA content with radioimmunoassay and high-performance liquid chromatography .
     Results:⑴Compared with the normal group, the body weight of high aggressive(HA) and low aggressive(LA) rats lessened significantly(P<0.001),while drenal glands coefficient of HA and LA rats’reduced (P<0.01).
     ⑵In aggressive behavior test, composite aggressive counts of HA rats were significantly higher than LA(P<0.001, P<0.001),latent time of attack were lower(P<0.001, P<0.001);In open-field experiment HA/LA rats’total scores were also higher than controlled (P<0.01), and HA rats’higher than LA’s, while comparison result of sugar preference coefficients contrary to it (P<0.01);
     ⑶Compared with anger-in group, Cor contents in serum of anger-out model rats descended notably(P<0.01),while NE contents increased(P<0.05); After administrated with Jingqianping (Jingqianshu) granule, abnormal fluctuations of 5-HT are obviously corrected between anger-out and anger-in (P<0.05).
     Compared with the control group, NE contents in hypothalamus, parietal region and hippocampus of anger model decreased (P<0.001), while DA contents in hypothalamus, and then restored after administration. Unlikely, DA contents in prefrontal cortex decreased (P<0.01), but increased in hypothalamus, they could both be corrected after administration. DA contents of anger-out model rats in prefrontal cortex and hippocampus were lower than anger-in group (P<0.001).
     Compared with the control group, 5-HT contents in hypothalamus of anger model rats degraded significantly (P<0.001), while increased in prefrontal cortex and decreased in hypothalamus, the abnormality disappeared after administration. 5-HT contents of anger-out model group in hypothalamus were obviously higher than anger-in group (P<0.05).
     Conclusion: The anger-out/in emotional reaction rat model can be introduced by the method of social isolation plus resident intruder stress. Modeling method was reliable and mature with a better credibility and repeatability; Adopting method aggressive behavior could distinguish anger-out/in belongings of rats’model clearly.
     Parts of the microcosmic mechanism were disclosed: anger-out emotion maybe related to NE, 5-HT level descending in hypothalamus, DA level descending in prefrontal cortex, parietal cortex and hippocampus, DA level increasing hypothalamus;while anger-in emotion maybe related to NE level increasing in parietal cortex and hippocampus,DA level increasing in hypothalamus, 5-HT level increasing in prefrontal cortex, 5-HT,NE level descending in hypothalamus, DA level descending in prefrontal cortex. We can assume that Jingqianping (Jingqianshu) granule play the role of pharmacological effects by corrected those indicators and its possible function location is different cerebral regions.
引文
[1]殷大奎.齐心协力脚踏实地全面推进新世纪精神卫生工作[J].中国心理卫生杂志,2002;16(1):4.
    [2]乔明琦,张惠云,王海军.愤怒和郁怒与经前期综合征肝气逆证肝气郁证相关性研究[J].陕西中医,2006;27(11):1359-1361.
    [3]Spiel Berger, C D. State-Trait Anger ExpressionInventory:Professional Manual[M]. Odessa, Florida: Psychological Assessment Resources, Inc.,1988
    [4] Spielberger, C.D. State-Trait Anger Expression Inventory -2. Odessa, Fl: Psychol- ogical Assessment Resource Inc. 1999.
    [5] Wei S,Zhang H,Gao J,et al.Impact of social isolation and resident intruder stress on aggressive behavior in the male rat[J].Neural Regen Res,2010;5(15): 1175-1179.
    [6] Grippo AJ, Lamb DG, Carter CS, Porges SW. Social isolation disrupts autonomic regulation of the heart and influences negative affective behaviors[J].Biol Psychiatry ,2007;62(10):1162-1170.
    [7]Rygula R,Abumaria N,Flügge G,et a1.Anhedonia and motiva- tional deficits in rats:Impact of chronic social stress[J].Behavioural Brain Research,2005;(162):127-134.
    [8] Rygula R,Abumaria N,Domenici E,Hiemke C,Fuchs E.Effects of fluoxetine on behavioral dficits evoked by chronic social stress in rats[J].Behavioural Brain Research,2006;174(1):188-192.
    [9] Ho HP, Olsson M, Westberg L, Melke J, Eriksson E. The serotonin reuptake inhibitor fluoxetine reduces sex steroid-related aggression in female rats: an animal model of premenstrual irritability[J].Neuropsychopharmacology,2001; 24(5):502-510.
    [10]Pandey DK, Mahesh R, Kumar AA, et al. A novel 5-HT(2A) receptor antagonist exhibits antidepressant-like effects in a battery of rodent behavioural assays: approaching early-onset antidepressants[J]. Pharmacol Biochem Behav,2010;94(3): 363-373.
    [11]赵云,杨发青,钱令嘉,等.应激对机体脑体功能的影响及其生物学机制初探[J].中国应用生理学杂志,2009;25(2):166-169.
    [12]张红梅,刘晓伟,曲宏达,等.愤怒心理应激动物模型的制作与行为学评估[J].中国行为医学科学,2005;14(2):188-190.
    [13]岳文浩,付文清,等.“怒伤肝”机制研究[J].医学与哲学,1995;16(9):481-483.
    [14]李杰,刘长江,李庆和,等.心理应激对大鼠下丘脑、胃粘膜CRF基因表达的影响及中药干预的实验研究[J].中医杂志,2002;43(9):699-700.
    [15] Qiao M,Zhao Q,Zhang H,et al.Isolating with physical restraint low status female monkeys during luteal phase might make an appropriate premenstrual depression syndrome model[J].J Affect Disord,2007;102(1-3):81-91.
    [16]须惠仁,傅湘琦,向丽华,等.肝郁证的动物实验研究[J].中医杂志,1991;1(6): 44-46.
    [17]顾立刚,王庆国,等.激怒刺激对大鼠下丘脑单胺类激素和T淋巴细胞功能变化影响的研究[J].中国中医药信息杂志,2000;7(8):44-45.
    [18] Guidotti A,Dong E,Matsumoto K,et al. The socially-isolated mouse:a model to study the putative role of allopregnanolone and 5alpha-dihydroprogesterone in psychiatric disorders[J]. Brain Res Brain Res Rev,2001;37(1-3):110-115.
    [19] Kaj Bjorkqvist. Social defeat as a stressor in humans[J]. Physiol Behav,2001; 73:435-42.
    [20] Peter van Meer, Jacob Raber. Mouse behavioural analysis in systems biology[J]. Biochem.J,2005;389:593-610.
    [21] Tanaka, M. Stress and alcohol: research with experimental animals[J].Nihon Arukoru. Yakubutsu Igakkai Zasshi,1998;33(1):31-43.
    [22]吴先哲.几种常用心理性胃粘膜损伤动物模型评述[J].湖北中医杂志,2002; 24(3):52-53.
    [23] Blanchard RJ.DC Blanchard.Aggressive behavior in the rat[J].Behav Biol,1977; 21(2):197-224.
    [24] Miczek KA.Tolerance to the analgesic,but not discriminative stimulus effects of morphine after brief social defeat in rats[J].Psychophannaeology (Bed),1991;104 (2):181-186.
    [25] Albonetti ME,Farabollini F.Social stress by repeated defeat:Effects on socialbehavior and emofionality[J].Brain research,1994;62(2):187-193.
    [26] Breuer ME, McGinnis MY, Lumia AR,et al. Aggression in male rats receiving anabolic androgenic steroids : effects of social and nvironment provocation[J]. Horm Behav,2001;40:409-418.
    [27] de Boer SF, Koolhaas JM.5-HT1A and 5-HT1B receptor agonists and aggression: A pharmacological challenge of the serotonin deficiency hypothesis[J]. Eur J Pharmacol,2005;5;526(1-3):125-139.
    [28] Pinna G, Dong E, Matsumoto K,et al.In socially isolated mice,the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine[J].Proc Natl Acad Sci USA,2003;100(4):2035-2040.
    [29] Nikulina EM, Arrillaga-Romany I, Miczek KA,et al. Long-lasting alteration in mesocorticolimbic structures after repeated social defeat stress in rats:time course ofμ-opioid receptor mRNA and FosB/DeltaFosB immunoreactivity[J]. Eur J Neurosci,2008;27(9):2272-2284.
    [30] Galina B.Vishnivetskaya, Galina B,et al. Effect of MAO A Deficiency on Differ- ent Kinds of Aggression and Social Investigation in Mice[J]. Aggressive behav,2007;33:1-6.
    [31] Fyffe SL, Neul JL, Samaco RC, et al. Deletion of Mecp2 in Sim1-expressing neurons reveals a critical role for MeCP2 in feeding behavior, aggression, and the response to stress[J]. Neuron,2008;59(6):947-958.
    [32] Pletzer B, Klimesch W, Oberascher-Holzinger K,et al. Corticoste- rone response in a resident-intruder-paradigm depends on social state and coping style in adolescent male Balb-C mice[J].Neuro Endocrinol Lett, 2007;28(5):585-590.
    [33] Vidal J, Bie J, Granneman RA, et al.Social stress during adolescence in Wistar rats induces social anxiety in adulthood without affecting brain monoaminergic content and activity[J]. Physiol Behav,2007;92(5): 824-830.
    [34]刘艳梅,祁红,陈红专.抗抑郁症药物治疗靶标的研究进展[J].中国新药与临床杂志,2005;24(10):764-766. [ 35 ]Muscat R, Willner P. Suppression of sucrose drinking by chronic mild unpredictable stress: a methodological analysis[J].Neurosci Biobehav Rev,1992;16:507-517.
    [36]Sapolsky RM,Romero LM, Munck AU. How do glucocorticoids in?uence stressresponses? Integrating permissive, suppressive, stimulatory, and preparative actions[J].Endocrinol Rev,2000;21:55-89.
    [37]Gr?nli J,Murison R,Bjorvatn B,et al.Chronic mild stress affects sucrose intake and sleep in rats[J].Behav Brain Res,2004;150(1-2):139-147.
    [38]Wang SH,Zhang ZJ,Guo YJ,et al.Anhedonia and activity deficits in rats: impact of post-stroke depression[J].J Psychopharmacol,2009;23(3):295-304.
    [39]方肇勤.辨证论治实验方法学-实验小鼠诊法与辨证[M].上海:上海科学技术出版社,2006:155-157.
    [40]Kessel B.Premenstrual syndrome. Advances in diagnosis and treatment[J].Obstet Gynecol Clin NorthAm.2000;27:(6)25-39.
    [41]Katz RJ,Roth KA,Carroll BJ.Acute and chronic stress effects on open field active- ity in the rat: implications for a model of depression[J].Neurosci Biobehav Rev,1981;5:247–251.
    [42]Keeney AJ,Hogg S.Behavioural consequences of repeated social defeat in the mouse: preliminary evaluation of a potential animal model of depression[J].Behav Pharmacol,1999;10:753–764.
    [43]Puglisi-Allegra S,Kempf E,Schleef C,et al.Repeated stressful experiences differ- ently affect brain dopamine receptor subtypes[J].Life Sci,1991;48:1263-1268.
    [44]Harris RB, Zhou J, Youngblood BD,et al.Failure to change exploration or saccharin preference in rats exposed to chronic mild stress[J].Physiol Behav,1997;63(1):91-100.
    [45]Willner P, Muscat R, Papp M. Chronic mild stress-induced anhedonia: a realistic animal model of depression[J].Neurosci Biobehav Rev,1992;16:525–534.
    [46] Corap?io?lu A, Erdo?an S. A cross-sectional study on expression of anger and factors associated with criminal recidivism in prisoners with prior offences[J]. Forensic Sci Int,2004;140(2-3):167-174.
    [47] Smith P, Waterman M, Ward N. Driving aggression in forensic and non-forensic populations: relationships to self-reported levels of aggression, anger and impulsivity[J]. Br J Psychol,2006;97(3):387-403.
    [48]徐叔云,卞如濂,陈修.药理实验方法学[M].北京:人民卫生出版社,2002,第三版:202-203.
    [49] Tong Y,Zou J,Ni LQ,et al.The effect of four kinds of traditional Chinese herbal compound on the experimental acute stress behaviors and the hypothala mus-pituitary-adrenal gland axis[J]. Zhongguo Zhong Yao Za Zhi,2005;30(23): 1863-1836.
    [50]文江平,唐爱国.HPLC快速测定血清中的芳香族氨基酸[J].中国色谱杂志, 2003;21(2):155-157.
    [51]刘钺,李思成,王枢,等.HPLC色谱-电化学检测法测定大鼠下丘脑单胺类神经递质[J].实用中西医结合杂志,1997;10(21):2062-2063.
    [52]曹日吕.普通心理学[M].北京:人民教育出版社,1996,354.
    [53]邵阳,谢斌,张明岛.“状态-特质愤怒”理论概念及其临床研究现状[J].上海精神医学,2010;22(2):109-111.
    [54] Davidson lt J,Jackson D C.Kalin N H.Emotion plasticity context and regulation: perspectives from affective neuroscience[J]. Psychological Bulletin,2000;126(6): 890-909.
    [55]吴斌.大鼠杏仁核-下丘脑神经通路研究[J].自然科学杂志,2000;201(1): 75-77.
    [56]黄伟秋.下丘脑在心血管调节中的作用[J].生理科学进展,1986;17(1): 25-28.
    [57]姚泰.生理学[M].5版.北京:人民卫生出版社,2000:356-358.
    [58]张宁霞,童瑶.应激对海马结构和功能影响的研究进展[J].中华国际医学杂志,2002;2(6):542-544.
    [59] Buckley PF.The Role of Typical and Atypical Antipsychotic Medications in the Management of Agitation and Aggression [J].J Clin Psychiatry,1999;60(10):52-60.
    [60] Dolan M, Anderson IM, Deakin JF. Relationship between 5-HT function and impulsivity and aggression in male offenders with personality disorders [J].Br J Psychiatry,2001;178:352-359.
    [61] Frye CA, Rhodes ME,Walf A,et al.Testosterone enhances aggression of wild-type mice but not those deficient in type I 5α-reductase[J].Brain Researeh,2002;948 (1-2):165-170.
    [62]余毅震,黄艳,史俊霞.青少年攻击行为与内分泌因素关系的研究[J].中国妇幼保健, 2007;22(14):1909-1911.
    [63] Tarter RE, Blackson T, Brigham J,et al. The association between childhood irritability and liability to substance use in early adolescence: a 2-year follow-up study of boys at risk for substance abuse [J]. Drug Alcohol Depend,1995;39(3):253-261.
    [64] Pajer K, Gardner W, Rubin RT,et al. Decreased cortisol levels in adolescent girls with conduct disorder[J]. Arch Gen Psychiatry. 2001;58(3):297-302.
    [65] McBurnett K, Lahey BB, Rathouz PJ, Loeber R. Low salivary cortisol and persistent aggression in boys referred for disruptive behavior[J]. Arch Gen Psychiatry,2000;57(1):38-43.
    [66]Albeck DS, McKittric CR, Blanchard CD,et al.Chronic social stress alters levels of cortico-trophin-releasing factor and arginine vasopressin mRNA in rat brain[J].J Neurosci,1997;17:4895-4903.
    [67] Nelson RJ, Chiavegatto S.Molecular basis of aggression[J].Trends Neurosci. 2001;24(12):713-719.
    [68]牛峰,甘景梨,高存友.攻击和暴力行为相关因素研究进展[J].临床心身疾病杂志,2006;12(3):232-234.
    [69] Bruner HG,Neiten M,Brakefield Xo,et al.Abnormal behaviour assoc- iated with a pointmutation in the structural gene for monoamine oxidase A[J].Science,1993;262:578-583.
    [70] Nagaoka S,lwamoto N,Arai H.First-episode neurolepic-free schizophrenics: con- centrations of monoamines and their metabolites in plasma and their correlation clinical responses to haloperidol treatment[J].Biological Psychiatry,1997;41(8): 857-864.
    [71] Anitole-Misleh KG, Brown KM.Developmental regulation of catecholamine Ievels during sea urchin embryo,morphogenesis[J]. Comp Biochem Physiol A Mol Integr Physiol,2004;137(1):39-50.
    [72] Sakaue M,Ago Y,Mruakami C,et al.Involvement of benzodinzepine binding sites in and antiaggressive effect by 5-HT1A receptor activation isolation mice[J].Eur J Pharmacol,2001;432(2-3):163-168.
    [73]龚绍麟.抑郁症[M].北京:人民卫生出版社,2003,1:97.
    [74]孙蓉,吕丽莉,郭守东,等.芍药苷对局灶性脑缺血模型及血脑屏障的影响[J].哈尔滨商业大学学报(自然科学版),2005;2l(4):405-410.
    [75]黄险峰,彭国平.香附的化学成分及药理研究进展[J].中药材,2003;26(1):65-68.
    [76]杨志刚,陈阿琴,孙红祥,等.柴胡皂苷药理作用研究进展[J].中国兽药杂志, 2005;39 (5):27-30.
    [77]戈宏焱,陈博,许丹.柴胡皂苷A对抑郁模型大鼠脑中单胺类神经递质及其代谢产物含量的影响[J].高等学校化学学报,2008;29(8):1535-1537.
    [78]王萍,陈青莲.柴胡炮制品对小白鼠全血胆碱酯酶活力的影响[J].中药材, 2000;23(4):219-220.
    [79]金顺姬.柴胡的药理作用及临床应用[J].现代医药卫生,2009;25(7):1074-1075.
    [80]王光明,周蓉.半夏的中药药理研究进展[J].中医药导报,2007;13(2):97-99.
    [1]蔡焯基.抑郁症—基础与临床[M].北京:科学出版社,2001:97
    [2]Florian H,Marcus I.Central CRH system in depression and anxiety evidence from clinical studies with CRH1 receptor antagonists[J].European Journal Pharmacol. 2008;583(2):350-357
    [3]Chali S,Okubo T,Sekighchi Y.Non-monoamine-based approach for the treatment of depression[J].Recent Patents on CNS Drug Discovery,2006;1(1):1-27
    [4]Rothermundt M, Arolt V, Fenker J,et al.Different immune patterns in melancholic and non-melancholic major depression[J]. Eur Arch Psychiatry Clin Neurosci, 2001;251(2):90-97.
    [5]Kessler RC, Chiu WT, Demler O, et al.Prevalence, severity, and comorbidity of 12- month DSM-IV disorders in the National Comorbidity Survey Replication[J]. Arch Gen Psychiatry, 2005;62(6):617-627.
    [6]Somers JM,Goldner EM,Waraich P, et al.Prevalence and incidence studies of anxi- ety disorders: a systematic review of the literature[J].Can J Psychiatry.2006;51(2): 100-113.
    [7]张朝卿.甘麦大枣汤治疗焦虑症[J].现代中西医结合杂志,1999;8(7):1108-1109
    [8]古全光,古燕萍.养心益胆法治疗焦虑性神经官能症73例[J].山东中医杂志, 2000;19(7):408-409.
    [9]朱晓旭,谢鸣.焦虑症中医药治疗研究现状(综述)[J].北京中医药大学学报,2002;25(3):63-65.
    [10]Hettema JM, Neale MC, Kendler KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders[J]. Am J Psychiatry, 2001;158(10):1568-1578.
    [11]Steiner M, Macdougall M, Brown E. The premenstrual symptoms screening tool (PSST) for clinicians[J]. Arch Womens Ment Health,2003;6(3):203-209.
    [12]Halbreich U, Borenstein J, Pearlstein T,et al.The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD)[J]. Psychoneuroen- docrinology,2003;28(3):1-23.
    [13]乔明琦.经前期综合征证候分布规律的流行病学调查研究[J].中国中医基础医学杂志,1997;(3):31.
    [14]Abraham GE.Nutritional factors in the etiology of the premenstrual tension syn-drome[J].J Reprod Mcd.1983;28(7):446-464.
    [15]Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic- pituitary-adrenal axis and the female reproductive system: clinical implications[J]. Ann Intern Med.1998,1;129(3):229-240.
    [16]Porsolt RD,LePichon M,Jalfre M,et al.Depression: a new animal model sensitive to antidepressant treatments[J]. Nature,1977;266:730-732.
    [17]Lucki I.The forced swimming test as a model for core and component behavioral effects of antidepressant drugs[J]. Behav Pharmacol 1997;8:523-532.
    [18]Renard CE,Dailly E,David DJ,et al.Monoamine metabolism changes following the mouse forced swimming test but not the tail suspension test[J].Fundam Clin Pharmacol 2003;17(4):449-455.
    [19]Steru L,Chermat R,Thierry B,et al.The tail suspension test: a new method for screening antidepressants in mice[J]. Psychopharmacology (Berl),1985;85: 367-370.
    [20]Cryan JF,Mombereau C,Vassout A.The tail suspension test as a model for assessi- ng antidepressant activity: review of pharmacological and genetic studies in mice [J].Neurosci Biobehav Rev,2005;29(4-5):571-625.
    [21]Cryan JF,Mombereau C.In search of a depressed mouse:utility of models for stud- ying depression-related behavior in genetically modified mice[J].Mol Psychiatry, 2004;9:326-357.
    [22]Dulawa SC,Hen R.Recent advances in animal models of chronic antidepressant effects: the novelty-induced hypophagia test[J].Neurosci Biobehav Rev,2005;29(4-5):771-783.
    [23]Deussing JM.Animal models of depression[J].Drug Discov Today Dis Models, 2006;3(4):375-383.
    [24] Bekris S, Antoniou K, Daskas S,et al. Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains[J]. Behav Brain Res,2005;3,161(1):45-59.
    [25]夏军,叶慧,周义成,等.慢性应激大鼠抑郁模型的建立及其有效性的探讨[J].华中科技大学学报:医学版,2005;34(4):493-494.
    [26]Willner P.Validity, reliability and utility of the chronic mild stress model of depression: a 10 year review and evaluation[J].Psychopharmacology (Bed),1997;134(4):319-329.
    [27]Varlinskaya EI, Spear LP, Spear NE. Social behavior and social motivation in adolescent rats: role of housing conditions and partner's activity[J].Physiol Behav, 1999;67(4):475-482.
    [28]Malkesman O,Maayan R,Weizman A,et al. Aggressive behavior and HPA axis hormones after social isolation in adult rats of two different genetic animal models for depression[J].Behav Brain Res,2006;175(2):408-414.
    [29]Pryce CR,Rüedi-Bettschen D,Dettling AC,et al. Long-term effects of early-life environmental manipulations inrodents and primates: potential animal models in depression research[J].Neurosci Biobehav Rev,2005;29(4-5):649-674.
    [30]Karten YJ, Olariu A, Cameron HA. Stress in early life inhibits neurogenesis in adulthood[J].Trends Neurosci,2005;28(4):171-172.
    [31]吕俊华,库宝善.电刺激小鼠角膜诱发的不动状态(一种新的抗抑郁药物研究动物模型)[J].北京医科大学学报,1990;22(5):354-355.
    [32]Harkin A,Kelly JP,Leonard BE.A review of the relevance and validity of olfactory bulbectomy as a model of depression[J].Clin Neurosci Res,2003;3(4-5):253-262.
    [33]Bondi M,Caretta A.Animal models of depression: olfactory lesions affect amygd- ala, subventricular zone, and aggression[J].Neurobiol Dis, 2004;16(2): 386-395.
    [34]McArthur R,Borsini F.Animal models of depression in drug discovery: a history- ical perspective[J].Pharmacol Biochem Behav,2006;84(3):436-452.
    [35] Duman RS, Malberg J, Nakagawa S. Regulation of adult neurogenesis by psychotropic drugs and stress[J]. J Pharmacol Exp Ther,2001;299(2):401-407.
    [36]郑丽芳,明亮.抑郁症动物模型的研究与应用[J].安徽医药,2005;9(11):801-803.
    [37]Solberg LC,Olason SL,Turek FW.Altered hormone levels and circadian rhythm of activity in the WKY rat,a putative animal model of depression[J].Am J Physiol Regul Integr Comp Physiol,2001;281(3):405-412.
    [38]Lavi-Avnon Y,Yadid G,Overstreet DH,et al.Abnormal patterns of maternal beha- veior in a genetic animal model of depression[J]. Physiol Behav,2005;84(4): 607-615.
    [39]郭建友,李昌煜,葛卫红,等.抑郁症动物模型研究进展[J].中国临床康,2004; 8(10):1932-1933.
    [40]Chourbaji S,Gass P.Glucocorticoid receptor transgenic mice as models for depre- sssion[J].Brain Res Rev,2008;57(2):554-560.
    [41]Ridder S,Chourbaji S,Hellweg R,et al.Mice with genetically altered glucocortic- oid receptor expression show altered sensitivity for stress-induced depressive reactions[J].J Neurosci,2005;25(26):6243- 6250.
    [42]Boyle MP,Kolber BJ,Vogt SK,et al.Forebrain glucocorticoid receptors modulate anxiety-associated locomotor activation and adrenal responsiveness[J].J Neurosci, 2006;26(7):1971-1978.
    [43]Meehan AO , Moran PM,Elliot JM,et al.A study of the effect of a single neurot- oxic dose of MDMA(ecstasy) on the subsequent long-term behaviour of rats in the plus maze and open field[J].Psychopharmacology,2002;159:167-175.
    [44]Kr?mer SA, Kessler MS, Milfay D,et al.Identification of glyoxalase-I as a protein marker in a mouse model of extremes in trait anxiety[J]. J Neurosci,2005;27;25 (17):4375-4384.
    [45]Treit D,Fundytus M. Thigmotaxis as a test for anxiolytic activity in rats[J]. Phar- mocol Biochem Behav,1988;31:959-962
    [46]Crawley JN.Exploratory behaviour models of anxiety in mice[J].Neurosci Biobe- hav rev,1985;9:27-44.
    [47]Huot RL, Thrivikraman KV, Meaney MJ, Plotsky PM.Development of adult ethanol preference and anxiety as a consequence of neonatal maternal separation in Long Evans rats and reversal with antidepressant treatment[J]. Psychopharmacology (Berl),2001;158(4):366-373.
    [48]Wigger A, Neumann ID.Periodic maternal deprivation induces gender-dependent alterations in behavioral and neuroendocrine responses to emotional stress in adult rats[J]. Physiol Behav,1999;66(2):293-302.
    [49]Treit D,Menard J,Pesold C.The shock-probe burying test[J].Neurosci Protocols Module,1994;3:9-17.
    [50]Slattery DA, Neumann ID.Chronic icv oxytocin attenuates the pathological high anxiety state of selectively bred Wistar rats[J].Neuropharmacology,2010;58(1): 56-61.
    [51]Knapp DJ, Overstreet DH, Breese GR. Baclofen blocks expression and sensitize-ation of anxiety-like behavior in an animal model of repeated stress and ethanol withdrawal[J]. Alcohol Clin Exp Res,2007;31(4):582-595.
    [52]Schank JR, Liles LC, Weinshenker D.Norepinephrine signaling through beta- adrenergic receptors is critical for expression of cocaine-induced anxiety[J]. Biol Psychiatry,2008;63(11):1007-1012.
    [53]Mantella RC, Vollmer RR, Li X ,et al. Female oxytocin-deficient mice display enhanced anxiety-related behavior[J].Endocrinology, 2003;144(6):2291-2296.
    [54]乔明琦,张惠云,等.择时造模猕猴经前期“病证表现”及其评价[J],中国中医基础医学杂志,2002;8(7):59-60
    [55]高冬梅,乔明琦,张惠云,等.经前期综合征肝气郁证猕猴模型评价指标[J].中医杂志,2005;46(12):931-933.
    [56]乔明琦,张惠云,陈雨振,等.肝郁证动物模型研究的理论思考[J].中国医药学报, 1997;12(5):42-44.
    [57]孙世光,张惠云.经前舒颗粒对PMS肝气郁证大鼠额叶皮层和海马5-HT1A受体结合活性的影响[J].中国中药杂志,2009;34(5):635-637.
    [58]毛海燕,叶林,叶向荣.肝郁证大鼠中枢神经递质变化的观察[J].福建中药,2002; 33(2):17-18.
    [59]Marván ML, Chavez-Chavez L, Santana S.Clomipramine modifies fluctuations of forced swimming immobility in different phases of the rat estrous cycle[J].Arch Med Res,1996;27(1):83-86.
    [60]Marván ML, Santana S, Chávez Chávez L,et al.Inescapable shocks accentuate fluctuations of forced swimming immobility in different phases of the rat estrous cycle[J].Arch Med Res,1997;28(3):369-372.
    [61]Schneider T, Popik P. Attenuation of estrous cycle-dependent marble burying in female rats by acute treatment with progesterone and antidepressants[J]. Psychon- euroendocrinology ,2007; 32: 651-659.
    [62]Schneider T, Popik P. An Animal Model of Premenstrual Dysphoric Disorder Sensitive toAntidepressants [J]. Current Protocols in Neuroscience,2009;9.31: 1-10.
    [63]Ho HP,Olsson M,Westberg L,et al.The serotonin reuptake inhibitor fluoxetine reduces sex steroid-related aggression in female rats: an animal model ofpremenstrual irritability[J].Neuropsychopharmacology,2001;24(5):502-510.
    [64]Ho HP,Olsson M,Annerbrink K,et al.Association between estrus cycle- related aggression and tidal volume variability in female Wistar rats[J]. Psychoneuroen- docrinology,2004;29(8):1097-1100.
    [65]张惠云,乔明琦,高鲁霞,等.大鼠模拟经前期综合征(PMS)肝气逆证动情周期血清激素水平的测定[J].中药药理与临床,2000;16(3):46-47.
    [66]L?fgren M, Johansson IM, Meyerson B, et al.Withdrawal effects from progester- one and estradiol relate to individual risk-taking and explorative behavior in female rats[J].Physiol Behav,2009;96(1):91–97.
    [67]L?fgren M, Johansson IM, Meyerson B,et al.Progesterone withdrawal effects in the open field test can be predicted by elevated plus maze performance[J]. Horm Behav. 2006;50(2):208-215.
    [68]Gulinello M,Gong QH,Smith SS.Progesterone withdrawal increases the anxiolytic actions of gaboxadol:role of alpha4betadelta GABA(A) receptors [J].Neuroreport, 2003;14(1):43-46.
    [69]Smith SS,Gong QH,Li X,et al.Withdrawal from 3α-OH-5α-pregnan-20-One Using a Pseudopregnancy Model Alters the Kinetics of Hippocampal GABAA- Gated Current and Increases the GABAA Receptorα4 Subunit in Association with Increased Anxiety[J].J Neurosci,1998;18(14):5275-5284.
    [70]相宇,郝世凤,陈淑涛,等.经轻胶囊对类经前期综合征动物模型病理状态干预作用的研究[J].中国中医药科技,2005;12(4):218-220.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700