药学学报, 2021, 56(4): 949-965
引用本文:
兰嘉琦, 赵春阳, 吴镭, 冯新红, 王庆利, 彭英. 抗焦虑障碍药物非临床药效学评价体系探索[J]. 药学学报, 2021, 56(4): 949-965.
LAN Jia-qi, ZHAO Chun-yang, WU Lei, FENG Xin-hong, WANG Qing-li, PENG Ying. Evaluation of non-clinical anxiety disorder models[J]. Acta Pharmaceutica Sinica, 2021, 56(4): 949-965.

抗焦虑障碍药物非临床药效学评价体系探索
兰嘉琦1, 赵春阳2, 吴镭1, 冯新红3, 王庆利2*, 彭英1*
1. 中国医学科学院、北京协和医学院药物研究所, 北京 100050;
2. 国家药品监督管理局药品审评中心, 北京 100022;
3. 清华大学附属北京清华长庚医院神经内科, 北京 102218
摘要:
焦虑障碍(anxiety disorder)是常见的成人精神障碍,其发病是遗传与环境因素共同作用的结果。基于焦虑障碍的发病机制,已经建立了一系列测量焦虑情绪水平和诱导焦虑情绪的动物模型,并广泛应用于抗焦虑药物筛选。本综述主要介绍了焦虑障碍的研究进展,对典型的动物模型体系进行归纳,包括既可以测量焦虑情绪水平也可以诱导焦虑情绪的动物模型和只诱导焦虑情绪的动物模型。本文总结了规范化焦虑障碍动物模型在非临床研究中需要注意的问题,并对抗焦虑药物的非临床药效学研究方案的系统化和规范化提出建议。
关键词:    焦虑障碍      动物模型      行为学评价      非临床药效学评价      新药研发     
Evaluation of non-clinical anxiety disorder models
LAN Jia-qi1, ZHAO Chun-yang2, WU Lei1, FENG Xin-hong3, WANG Qing-li2*, PENG Ying1*
1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
2. Center for Drug Evaluation, National Medical Product Administration, Beijing 100022, China;
3. Department of Neurology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China
Abstract:
Anxiety disorders are one of the most common mental disorders in adults, the cause of which derives from a combination of genetics and environmental factors. A series of animal models have been established according to their pathogenesis to measure the level of anxiety or induce anxiety only, and these models have been widely applied in the non-clinical evaluation of anxiolytics. In this review, we present the current trends in the study of anxiety disorders and summarize typical non-clinical anxiety animal models, including models that both measure anxiety levels and induce anxiety, and models that induce anxiety only. This review summarizes the important issues in standardized non-clinical research of anxiety disorders and proposes criteria for the selection of an appropriate R&D model.
Key words:    anxiety disorder    animal model    behavioristics    non-clinical pharmacodynamics    drug discovery   
收稿日期: 2020-09-29
DOI: 10.16438/j.0513-4870.2020-1569
基金项目: 国家自然科学基金资助项目(81802877);中国医学科学院医-学与健康科技创新工程(2017-I2M-2-004);国家“重大新药创制”科技重大专项(2018ZX09711001-003-005,2018ZX09711001-003-009).
通讯作者: 彭英,Tel:86-10-83165742,Fax:86-10-63017757,E-mail:ypeng@imm.ac.cn;王庆利,Tel:86-10-68585566,Fax:86-10-68584189,E-mail:wangql@cde.org.cn
Email: ypeng@imm.ac.cn;wangql@cde.org.cn
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参考文献:
[1] Association AP. Diagnostic and statistical manual of mental disorders[J]. BMC Med, 2013, 17:133-137.
[2] Bandelow B, Baldwin D, Abelli M, et al. Biological markers for anxiety disorders, OCD and PTSD-a consensus statement. Part I:neuroimaging and genetics[J]. World J Biol Psychiatry, 2016, 17:1-45.
[3] Shao F, Lin W, Wang W, et al. The effect of emotional stress on the primary humoral immunity of rats[J]. J Psychopharmacol, 2003, 17:179-183.
[4] Baxter A, Scott K, Vos T, et al. Global prevalence of anxiety disorders:a systematic review and meta-regression[J]. Psychol Med, 2013, 43:897-910.
[5] Hantsoo L, Epperson CN. Anxiety disorders among women:a female lifespan approach[J]. Focus (Am Psychiatr Publ), 2017, 15:162-172.
[6] Huang YQ, Wang Y, Wang H, et al. Prevalence of mental disorders in China:a cross-sectional epidemiological study[J]. Lancet Psychiatry, 2019, 6:211-224.
[7] Linden W, Vodermaier A, MacKenzie R, et al. Anxiety and depression after cancer diagnosis:prevalence rates by cancer type, gender, and age[J]. J Affect Disord, 2012, 141:343-351.
[8] McWilliams LA, Cox BJ, Enns MW. Mood and anxiety disorders associated with chronic pain:an examination in a nationally representative sample[J]. Pain, 2003, 106:127-133.
[9] Broen MP, Narayen NE, Kuijf ML, et al. Prevalence of anxiety in Parkinson's disease:a systematic review and meta-analysis[J]. Mov Disord, 2016, 31:1125-1133.
[10] Barker-Collo SL. Depression and anxiety 3 months post stroke:prevalence and correlates[J]. Arch Clin Neuropsychol, 2007, 22:519-531.
[11] Shimada-Sugimoto M, Otowa T, Hettema JM. Genetics of anxiety disorders:genetic epidemiological and molecular studies in humans[J]. Psychiatry Clin Neurosci, 2015, 69:388-401.
[12] Chen ZB, Zhang B, Min LX, et al. Research progress on the pathogenesis of anxiety[J]. Tianjin J Tradit Chin Med (天津中医药), 2018, 35:316-320.
[13] Schienle A, Hettema J, Caceda R, et al. Neurobiology and genetics of generalized anxiety disorder[J]. Psychiatr Ann, 2011, 41:113-123.
[14] Calhoon G, Tye K. Resolving the neural circuits of anxiety[J]. Nat Neurosci, 2015, 18:1394-1404.
[15] Fischer S, Ehlert U. Hypothalamic-pituitary-thyroid (HPT) axis functioning in anxiety disorders. A systematic review[J]. Depress Anxiety, 2018, 35:98-110.
[16] Maeng LY, Milad MR. Sex differences in anxiety disorders:interactions between fear, stress, and gonadal hormones[J]. Horm Behav, 2015, 76:106-117.
[17] Gawali NB, Bulani VD, Gursahani MS, et al. Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway[J]. Brain Res, 2017, 1663:66-77.
[18] Sharma S, Powers A, Bradley B, et al. Gene×environment determinants of stress- and anxiety-related disorders[J]. Annu Rev Psychol, 2016, 67:239-261.
[19] Qi XL, Lin WJ. Methods and strategies of anxiety and depression animal models study[J]. Adv Psychol Sci (心理科学进展), 2005, 13:327-332.
[20] Fava GA, Sonino N, Morphy MA. Psychosomatic view of endocrine disorders[J]. Psychother Psychosom, 1993, 59:20-33.
[21] Hogle JM, Kaye JT, Curtin JJ. Nicotine withdrawal increases threat-induced anxiety but not fear:neuroadaptation in human addiction[J]. Biol Psychiatry, 2010, 68:719-725.
[22] Uhde TW, Tancer ME, Gurguis GN. Chemical models of anxiety:evidence for diagnostic and neurotransmitter specificity[J]. Int Rev Psychiatry, 1990, 2:367-384.
[23] Katzman MA, Bleau P, Blier P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders[J]. BMC Psychiatry, 2014, 14:S1.
[24] Zhang HY, Li YZ. Tandospirone, an emergingdrugs for the treatment of general anxiety disorders[J]. Clin Med J (临床药物治疗杂志), 2005, 3:53-57.
[25] Su H, Jiang KD, Xu YF. 5-Serotonin and norepinephrine reuptake inhibitor is first line drug for anxiety disorder[J]. Chin J New Drugs Clin Rem (中国新药与临床杂志), 2010, 29:264-269.
[26] Wu WY. Guidelines for the Prevention and Treatment of Anxiety Disorders (焦虑障碍防治指南)[M]. Beijing:People's Medical Publishing House, 2010.
[27] Bourin M. Animal models for screening anxiolytic-like drugs:a perspective[J]. Dialogues Clin Neurosci, 2015, 17:295-303.
[28] Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors:a review[J]. Eur J Pharmacol, 2003, 463:3-33.
[29] Wei W, Wu XM, Li YJ. Experimental Methodology of Pharmacology (药理学实验方法学)[M]. Beijing:People's Medical Publishing House, 2010.
[30] Bailey KR, Crawley JN. Chapter 5. Anxiety-related behaviors in mice[M]//Jerry J Buccafusco.Methods of Behavior Analysis in Neuroscience. Boca Raton:2CRC Press/Taylor & Francis, 2009.
[31] Fromm L, Heath DL, Vink R, et al. Magnesium attenuates post-traumatic depression/anxiety following diffuse traumatic brain injury in rats[J]. J Am Coll Nutr, 2004, 23:529S-533S.
[32] Salum C, Roque-da-Silva AC, Morato S. Conflict as a determinant of rat behavior in three types of elevated plus-maze[J]. Behav Processes, 2003, 63:87-93.
[33] Pellow S, Chopin P, File SE, et al. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat[J]. J Neurosci Methods, 1985, 14:149-167.
[34] Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents[J]. Nat Protoc, 2008, 2:322-328.
[35] Kumar V, Bhat ZA, Kumar D. Animal models of anxiety:a comprehensive review[J]. J Pharmacol Toxicol Methods, 2013, 68:175-183.
[36] Shepherd JK, Grewal SS, Fletcher A, et al. Behavioural and pharmacological characterisation of the elevated "zero-maze" as an animal model of anxiety[J]. Psychopharmacology (Berl), 1994, 116:56-64.
[37] Cook MN, Crounse M, Flaherty L. Anxiety in the elevated zero-maze is augmented in mice after repeated daily exposure[J]. Behav Genet, 2002, 32:113-118.
[38] Crawley JN. Exploratory behavior models of anxiety in mice[J]. Neurosci Biobehav Rev, 1985, 9:37-44.
[39] Boissier J. La reaction d'exploration chez la souris[J]. Therapie, 1962, 17:1225-1232.
[40] File SE, Wardill AG. Validity of head-dipping as a measure of exploration in a modified hole-board[J]. Psychopharmacologia, 1975, 44:53-59.
[41] Kalueff AV, Keisala T, Minasyan A, et al. The regular and light-dark Suok tests of anxiety and sensorimotor integration:utility for behavioral characterization in laboratory rodents[J]. Nat Protoc, 2008, 3:129-136.
[42] File SE, Hyde J. Can social interaction be used to measure anxiety?[J]. Br J Pharmacol, 1978, 62:19.
[43] Sánchez C. Stress-induced vocalisation in adult animals. A valid model of anxiety?[J]. Eur J Pharmacol, 2003, 463:133-143.
[44] Iijima M, Chaki S. Separation-induced ultrasonic vocalization in rat pups:further pharmacological characterization[J]. Pharmacol Biochem Behav, 2006, 82:652-657.
[45] Lecci A, Borsini F, Volterra G, et al. Pharmacological validation of a novel animal model of anticipatory anxiety in mice[J]. Psychopharmacology (Berl), 1990, 101:255-261.
[46] Zhao YN, Du LJ. Experimental animal models of nervous system[M]//Du LJ, Zhao YN.Laboratory Animal and Experimental Animal Models (实验动物与实验动物模型). Beijing:China Medical Science Press, 2012:43-115.
[47] Han YW, Zhao LZ, Liu QQ, et al. Effect of conditioned fear training on behavioral activity in F344 rats[J]. Chin J Behav Med Sci (中华行为医学与脑科学杂志), 2004, 13:622-623.
[48] Bodnoff SR, Suranyi-Cadotte B, Aitken DH, et al. The effects of chronic antidepressant treatment in an animal model of anxiety[J]. Psychopharmacology (Berl), 1988, 95:298-302.
[49] Blasco-Serra A, González-Soler EM, Cervera-Ferri A, et al. A standardization of the novelty-suppressed feeding test protocol in rats[J]. Neurosci Lett, 2017, 658:73-78.
[50] Li CF, Chen XM, Chen SM, et al. Extracts from Pericarpium citri improve behaviors and hippocampal BDNF in mice exposed to chronic mild unpredictable stress[J]. China J Exp Tradit Med Form (中国实验方剂学杂志), 2014, 20:151-154.
[51] Pollard GT, Howard JL. Cork gnawing in the rat as a screening method for buspirone-like anxiolytics[J]. Drug Dev Res, 1991, 22:179-187.
[52] Campos AC, Fogaca MV, Aguiar DC, et al. Animal models of anxiety disorders and stress[J]. Braz J Psychiatry, 2013, 35:S101-S111.
[53] File SE, Lippa AS, Beer B, et al. Animal tests of anxiety[J]. Curr Protoc Neurosci, 2004, Chapter 8:Unit 8.3.
[54] Geller I, Seifter J. The effects of meprobamate, barbiturates, D-amphetamine and promazine on experimentally induced conflict in the rat[J]. Psychopharmacologia, 1960, 1:482-492.
[55] Spencer DG, Lal H. CGS 9896, a chloro-derivative of the diazepam antagonist CGS 8216, exhibits anxiolytic activity in the pentylenetetrazol-saline discrimination test[J]. Drug Dev Res, 1983, 3:365-370.
[56] Vogel JR, Beer B, Clody DE. A simple and reliable conflict procedure for testing anti-anxiety agents[J]. Psychopharmacologia, 1971, 21:1-7.
[57] Degroot A, Treit D. Dorsal and ventral hippocampal cholinergic systems modulate anxiety in the plus-maze and shock-probe tests[J]. Brain Res, 2002, 949:60-70.
[58] Vry JD, Benz U, Schreiber R, et al. Shock-induced ultrasonic vocalization in young adult rats:a model for testing putative anti-anxiety drugs[J]. Eur J Pharmacol, 1993, 249:331-339.
[59] Jelen P, Soltysik S, Zagrodzka J. 22-kHz Ultrasonic vocalization in rats as an index of anxiety but not fear:behavioral and pharmacological modulation of affective state[J]. Behav Brain Res, 2003, 141:63-72.
[60] Borta A, Wöhr M, Schwarting RKW. Rat ultrasonic vocalization in aversively motivated situations and the role of individual differences in anxiety-related behavior[J]. Behav Brain Res, 2006, 166:271-280.
[61] Estes WK, Skinner BF. Some quantitative properties of anxiety[J]. J Exp Psychol, 1941, 29:390.
[62] Davis M. Animal models of anxiety based on classical conditioning:the conditioned emotional response (CER) and the fear-potentiated startle effect[J]. Pharmacol Ther, 1990, 47:147-165.
[63] Dong XW, Wang CY, Wng CL, et al. The progress of startle paradigm in the clinical studies of PTSD:hyperarousal and fear inhibition[J]. Adv Psychol Sci (心理科学进展), 2013, 21:965-974.
[64] Geng DD, Bai WZ, Ma J, et al. c-fos expression in the parabrachial nucleus following differential conditioning taste aversion in rats[J]. Acta Psychol Sin (心理学报), 2006, 38:442-447.
[65] Ervin G, Soroko F, Cooper B. Buspirone antagonizes the expression of conditioned taste aversion in rats[J]. Drug Dev Res, 1987, 11:87-95.
[66] Lezak KR, Missig G, Carlezon WA. Behavioral methods to study anxiety in rodents[J]. Dialogues Clin Neurosci, 2017, 19:181-191.
[67] Gao WT, Yang C, Wang HY, et al. Physiological basis of the stress models and their progressin comparative study[J]. Prog Modern Biomed (现代生物医学进展), 2014, 14:4160-4163.
[68] Zhu MH, Jiang N, Zhou WX. Establishment and comparison of anxiety models by uncertain empty water bottle stimulation and restraint stress in mice[J]. Chin J Pharmacol Toxicol (中国药理学与毒理学杂志), 2019, 33:102-108.
[69] Beutel ME, Jünger C, Klein EM, et al. Noise annoyance is associated with depression and anxiety in the general population-the contribution of aircraft noise[J]. PLoS One, 2016, 11:e0155357.
[70] Tafet GE, Nemeroff CB. Pharmacological treatment of anxiety disorders:the role of the HPA axis[J]. Front Psychiatry, 2020, 11:443.
[71] Mitra R, Sapolsky RM. Acute corticosterone treatment is sufficient to induce anxiety and amygdaloid dendritic hypertrophy[J]. Proc Natl Acad Sci U S A, 2008, 105:5573-5578.
[72] Zhao HQ, Han YS, Liu Z, et al. Changes of control of monoamine neurotransmitters and expression of neurotrophic factors in brain regions of rat modals of anxious depression[J]. Acta Lab Anim Sci Sin (中国实验动物学报), 2017, 25:373-379.
[73] Gregus A, Wintink AJ, Davis AC, et al. Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats[J]. Behav Brain Res, 2005, 156:105-114.
[74] Wu MY, Qing ZH, Yang Q, et al. Study on model of tree shrew induced by chronic corticosterone injection in anxious depression[J]. Chin Pharmacol Bull (中国药理学通报), 2018, 34:141-144.
[75] Yang C, Feng GK. Review on modeling methods of anxious animal model[J]. J Guangzhou Univ Tradit Chin Med (广州中医药大学学报), 2015, 32:1135-1138.
[76] Evans J, Sun Y, Mcgregor A, et al. Allopregnanolone regulates neurogenesis and depressive/anxiety-like behaviour in a social isolation rodent model of chronic stress[J]. Neuropharmacology, 2012, 63:1315-1326.
[77] Liu YJ, Li LF, Bao WD, et al. Effects of chronic social isolation on behavior and physiology in female rats[J]. J Shaanxi Norm Univ:Nat Sci Ed (陕西师范大学学报(自然科学版)), 2016, 44:71-77.
[78] Weiss IC, Pryce CR, Jongenrelo AL, et al. Effect of social isolation on stress-related behavioural and neuroendocrine state in the rat[J]. Behav Brain Res, 2004, 152:279-295.
[79] Matsumoto K, Puia G, Dong E, et al. GABAA receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress:possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders[J]. Stress, 2007, 10:3-12.
[80] Lin WJ, Wang WW, Shao F. New animal model of emotional stress:behavioral, neuroendocrine and immunological consequences[J]. Chin Sci Bull, 2003, 48:1565-1568.
[81] Zhang HQ, Han YS, Du Q, et al. Research of different methods of stress-induced anxiety-like behavior in rats at different time points[J]. Chin J Comp Med (中国比较医学杂志), 2017, 27:22-26.
[82] Venzala E, Garcia-Garcia A, Elizalde N, et al. Chronic social defeat stress model:behavioral features, antidepressant action, and interaction with biological risk factors[J]. Psychopharmacology (Berl), 2012, 224:313-325.
[83] Golden S, Covington H, Berton O, et al. Corrigendum:a standardized protocol for repeated social defeat stress in mice[J]. Nat Protoc, 2011, 6:1183-1191.
[84] Kieran N, Ou XM, Iyo AH. Chronic social defeat downregulates the 5-HT1A receptor but not Freud-1 or NUDR in the rat prefrontal cortex[J]. Neurosci Lett, 2010, 469:380-384.
[85] Rygula R, Abumaria N, Flügge G, et al. Anhedonia and motivational deficits in rats:impact of chronic social stress[J]. Behav Brain Res, 2005, 162:127-134.
[86] Zhang YR, Wang RZ, Chen R, et al. Changes of Wnt/β-catenin signaling pathway in the hippocampus caused by prenatal stress induce depression- and anxiety-like behaviors in rats[J]. J South Med Univ (南方医科大学学报), 2019, 39:102-106.
[87] Dryden S, Wang Q, Frankish HM, et al. Differential effects of the 5-HT1B2C receptor agonist mCPP and the 5-HT1A agonist flesinoxan on hypothalamic neuropeptide Y in the rat:evidence that NPY may mediate serotonin's effects on food intake[J]. Peptides, 1996, 17:943-949.
[88] Tan DJ, Takenaga T, Otomo S. m-Chlorophenylpiperazine-induced anxiety model in light-dark box in ddy mice-a new economic and simple method for screening anxiolytics[J]. Acta Pharm Sin (药学学报), 2000, 35:580-582.
[89] Yeung M, Lu L, Hughes AM, et al. FG7142, yohimbine, and βCCE produce anxiogenic-like effects in the elevated plus-maze but do not affect brainstem activated hippocampal theta[J]. Neuropharmacology, 2013, 75:47-52.
[90] Jacobson LH, Cryan JF. Genetic approaches to modeling anxiety in animals[M]//Stein MB, Steckler T. Behavioral Neurobiology of Anxiety and Its Treatment. Berlin, Heidelberg:Springer Berlin Heidelberg, 2010:161-201.
[91] Finn DA, Rutledge-Gorman MT, Crabbe JC. Genetic animal models of anxiety[J]. Neurogenetics, 2003, 4:109-135.
[92] Olivier J, Van Der Hart M, Van Swelm R, et al. A study in male and female 5-HT transporter knockout rats:an animal model for anxiety and depression disorders[J]. Neuroscience, 2008, 152:573-584.
[93] Toth M. 5-HT1A receptor knockout mouse as a genetic model of anxiety[J]. Eur J Pharmacol, 2003, 463:177-184.
[94] Savage K, Firth J, Stough C, et al. GABA-modulating phytomedicines for anxiety:a systematic review of preclinical and clinical evidence[J]. Phytother Res, 2018, 32:3-18.
[95] Müller I, Çalışkan G, Stork O. The GAD65 knock out mouse-a model for GABAergic processes in fear- and stress-induced psychopathology[J]. Genes Brain Behav, 2015, 14:37-45.
[96] Watson S, Mackin P. HPA axis function in mood disorders[J]. Psychiatry, 2006, 5:166-170.
[97] Van Gaalen MM, Stenzel-Poore MP, Holsboer F, et al. Effects of transgenic overproduction of CRH on anxiety-like behaviour[J]. Eur J Neurosci, 2002, 15:2007-2015.
[98] Gass P, Reichardt HM, Strekalova T, et al. Mice with targeted mutations of glucocorticoid and mineralocorticoid receptors:models for depression and anxiety?[J]. Physiol Behav, 2001, 73:811-825.
[99] Wei Q, Fentress HM, Hoversten MT, et al. Early-life forebrain glucocorticoid receptor overexpression increases anxiety behavior and cocaine sensitization[J]. Biol Psychiatry, 2012, 71:224-231.
[100] Lin S, Boey D, Herzog H. NPY and Y receptors:lessons from transgenic and knockout models[J]. Neuropeptides, 2004, 38:189-200.
[101] Chen ZY, Jing D, Bath KG, et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior[J]. Science, 2006, 314:140-143.
[102] Ren-Patterson RF, Cochran LW, Holmes A, et al. Gender-dependent modulation of brain monoamines and anxiety-like behaviors in mice with genetic serotonin transporter and BDNF deficiencies[J]. Cell Mol Neurobiol, 2006, 26:753-778.
[103] Wilson W, Voigt P, Bader M, et al. Behaviour of the transgenic (mREN2) 27 rat[J]. Brain Res, 1996, 729:1-9.
[104] Voigt JP, Hörtnagl H, Rex A, et al. Brain angiotensin and anxiety-related behavior:the transgenic rat TGR(ASrAOGEN)680[J]. Brain Res, 2005, 1046:145-156.
[105] Barros M, Tomaz C. Non-human primate models for investigating fear and anxiety[J]. Neurosci Biobehav Rev, 2002, 26:187-201.
[106] Cagni P, Komorowski M, Melo GC, et al. Diazepam-induced decrease in anxiety-like behaviors of marmoset monkeys exposed to a novel open-field[J]. Pharmacol Biochem Behav, 2012, 100:518-521.
[107] Wang Y, Fang Q, Gong N. A modified light-dark box test for the common marmoset[J]. Neurosci Bull, 2014, 30:394-400.
[108] Jung YH, Hong SI, Ma SX, et al. Strain differences in the chronic mild stress animal model of depression and anxiety in mice[J]. Biomol Ther, 2014, 22:453.
[109] Rex A, Voigt JP, Gustedt C, et al. Anxiolytic-like profile in wistar, but not sprague-dawley rats in the social interaction test[J]. Psychopharmacology (Berl), 2004, 177:23-34.
[110] Marcondes FK, Miguel KJ, Melo LL, et al. Estrous cycle influences the response of female rats in the elevated plus-maze test[J]. Physiol Behav, 2001, 74:435-440.
[111] File SE, Wardill AG. The reliability of the hole-board apparatus[J]. Psychopharmacologia, 1975, 44:47-51.
[112] Palanza P. Animal models of anxiety and depression:how are females different?[J]. Neurosci Biobehav Rev, 2001, 25:219-233.
[113] Gallo MA, Smith SS. Progesterone withdrawal decreases latency to and increases duration of electrified prod burial:a possible rat model of PMS anxiety[J]. Pharmacol Biochem Behav, 1993, 46:897-904.
[114] Reis F, Pestana-Oliveira N, Leite CM, et al. Hormonal changes and increased anxiety-like behavior in a perimenopause-animal model induced by 4-vinylcyclohexene diepoxide (VCD) in female rats[J]. Psychoneuroendocrinology, 2014, 49:130-140.
[115] dela Peña IJI, Kim HJ, Botanas CJ, et al. The psychopharmacological activities of Vietnamese ginseng in mice:characterization of its psychomotor, sedative-hypnotic, antistress, anxiolytic, and cognitive effects[J]. J Ginseng Res, 2017, 41:201-208.
[116] Adeyemi OO, Yemitan OK, Taiwo AE. Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphia nitida AFZEL[J]. J Ethnopharmacol, 2006, 106:312-316.
[117] Hosseinzadeh H, Nassiri Asl M. Anticonvulsant, sedative and muscle relaxant effects of carbenoxolone in mice[J]. BMC Pharmacol, 2003, 3:3.
[118] Farouk L, Laroubi A, Aboufatima R, et al. Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.:possible mechanisms involved[J]. J Ethnopharmacol, 2008, 115:449-454.
[119] Naef M, Curatolo M, Petersen-Felix S, et al. The analgesic effect of oral delta-9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions[J]. Pain, 2003, 105:79-88.
[120] Ferrari F, Giuliani D. Behavioural assessment in rats of the antipsychotic potential of the potent dopamine D2 receptor antagonist, (-)eticlopride[J]. Pharmacol Res, 1995, 31:261-267.
[121] Sanberg PR, Bunsey MD, Giordano M, et al. The catalepsy test:its ups and downs[J]. Behav Neurosci, 1988, 102:748-759.
[122] Huang JZ, Wang ZC. Experimental methods and pharmacological evaluation of anxiety animal models[J]. Shanghai Arch Psychiatry (上海精神医学), 2003, 15:106-109.
[123] Treit D, Engin E, McEown K. Animal models of anxiety and anxiolytic drug action[M]//Stein MB, Steckler T. Behavioral Neurobiology of Anxiety and Its Treatment. Berlin, Heidelberg:Springer Berlin Heidelberg, 2010:121-160.
[124] Zhou JY, Zhou SW, Tang JL. Research progress on anti-anxiety effect of Chinese herbal compound preparations[J]. China Pharm (中国药房), 2010, 21:1044-1047.
[125] Lv YW, Guo JY, Liu Y, et al. Advanced in studies on anxiolytic effects of natural flavonoids[J]. China J Chin Mater Med (中国中药杂志), 2016, 41:38-44.
[126] Zhang YY, Wang JM, Cui Y, et al. Research progress of anxiolytic and antidepressant bioactive ingredients of Chinese medicine alkaloids and the pharmacological effect of Coptidis Rhizoma alkaloids[J]. China J Tradit Chin Med Pharma (中华中医药杂志), 2015, 30:1184-1187.
[127] Wang XH, Zhang CX, Li GY, et al. Review on anxiolytic effect of natural small-molecule phenols[J]. China J Chin Mater Med (中国中药杂志), 2017, 42:1557-1565.
[128] Qin WX, Guo ZZ, Jie HB, et al. Tolerance and safety of buagafuran in Chinese healthy volunteers[J]. Chin J New Drugs (中国新药杂志), 2011, 20:110-114.
[129] Chen X, Jiang J, Yang F, et al. Pharmacokinetic and pharmacodynamic studies on anxiolytic drug buagafuran[J]. Med J Peking Union Med Coll Hosp (协和医学杂志), 2013, 4:5-10.
[130] Zhang Y, Wang W, Zhang J. Effects of novel anxiolytic 4-butyl-alpha-agarofuran on levels of monoamine neurotransmitters in rats[J]. Eur J Pharmacol, 2004, 504:39-44.
[131] Li YF. Rapid onset antidepressant-anxiety target strategy and new drug research[J]. Chin J Pharmacol Toxicol (中国药理学与毒理学杂志), 2017, 31:473-474.
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