Update in the methodology of the chronic stress paradigm: internal control matters

Behavioral and Brain Functions

Tatyana Strekalova²  Yvonne Couch³  Natalia Kholod⁶  Marco Boyks¹  Dmitry Malin⁵  Pierre Leprince⁴  Harry MW Steinbusch¹ 

[1] Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands

[2] Center of Environmental Biology, Faculty of Sciences, Lisbon University, Lisbon, Portugal

[3] Department of Pharmacology, Oxford University, Oxford, UK

[4] GIGA-Neuroscience, University of Liege, Liege, Belgium

[5] Northwestern University, Feinberg School of Medicine, Lurie Cancer center, Chicago, IL, USA

[6] Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia

关键词: mouse;    neuroinflammation;    gene expression profiling;    antidepressant treatment;    anhedonia;    sucrose test;    chronic stress;    animal model of depression;   

Others  :  797647
DOI  :  10.1186/1744-9081-7-9

 received in 2010-07-18, accepted in 2011-04-27,  发布年份 2011

【 摘 要 】

To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stress-induced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals.

【 授权许可】

   
2011 Strekalova et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Lassnig R, Hofmann P: Life crisis as a consequence of depression and anxiety. Wien Med Wochenschr. [Article in German] 2007, 157:435-444.
• [2]Lexis M, Jansen N, van Amelsvoort L, van den Brandt P, Kant I: Depressive complaints as a predictor of sickness absence among the working population. J Occup Environ Med 2009, 5:887-895.
• [3]Kessler R, Chiu W, Demler O, Merikangas K, Walters E: Prevalence, severity and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005, 62:617-627.
• [4]Khandker R, Kruzikas D, McLaughlin T: Pharmacy and medical costs associated with switching between venlafaxine and SSRI antidepressant therapy for the treatment of major depressive disorder. J Manag Care Pharm 2008, 14:426-441.
• [5]Greenberg P, Corey-Lisle P, Birnbaum H, Marynchenko M, Claxton A: Economic implications of treatment-resistant depression among employees. Pharmacoeconomics 2004, 22:363-373.
• [6]Hamilton M: Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967, 6:278-296.
• [7]Klein D: Endogenomorphic depression. A conceptual and terminological revision. Arch Gen Psychiatry 1974, 31:447-454.
• [8]Insel TR: From animal models to model animals. Biol Psychiatry 2007, 15:1337-1339.
• [9]Krishnan V, Nestler EJ: Animal Models of Depression: Molecular Perspectives. Curr Top Behav Neurosci 2011, in press.
• [10]Cryan J, Holmes A: The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 2005, 4:775-790.
• [11]Willner P: Animal models as simulations of depression. Trends Pharmacol Sci 1991, 12:131-136.
• [12]Willner P: Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharm 1997, 134:319-329.
• [13]Willner P: Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiol 2005, 52:90-120.
• [14]Anisman H, Matheson K: Stress, depression and anhedonia: caveats concerning animal models. Neurosci & Biobehav Rev 2005, 29:525-546.
• [15]Katz R: Animal models and human depressive disorders. Neurosci Biobehav Rev 1981, 5:231-246.
• [16]Willner P, Towell A, Sampson D, Sophokleous S, Muscat R: Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology (Berl) 1987, 93:358-364.
• [17]Katz R: Animal model of depression: pharmacological sensitivity of a hedonic deficit. Pharmacol Biochem Behavior 1982, 16:965-968.
• [18]Moreau J, Scherschlicht R, Jenck F, Martin J: Chronic mild stress-induced anhedonia model of depression; sleep abnormalities and curative effects of electroshock treatment. Behav Pharmacol 1995, 6:682-687.
• [19]Baker S, Kentner A, Konkle A, Santa-Maria Barbagallo L, Bielajew C: Behavioral and physiological effects of chronic mild stress in female rats. Physiol Behav 2006, 87:314-322.
• [20]Grønli J, Murison R, Bjorvatn B, Sørensen E, Portas CM, Ursin R: Chronic mild stress affects sucrose intake and sleep in rats. Behav Brain Res 2004, 150:139-147.
• [21]Krishnan V, Han MH, Graham D, Berton O, Renthal W, Russo S, Laplant Q, Graham A, Lutter M, Lagace D, Ghose S, Reister R, Tannous P, Green T, Neve R, Chakravarty S, Kumar A, Eisch A, Self D, Lee F, Tamminga C, Cooper D, Gershenfeld H, Nestler E: Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 2007, 131:391-404.
• [22]Pothion S, Bizot J, Trovero F, Belzung C: Strain differences in sucrose preference and in the consequences of unpredictable chronic mild stress. Behav Brain Res 2004, 155:135-146.
• [23]Bergström A, Jayatissa MN, Thykjaer T, Wiborg O: Molecular pathways associated with stress resilience and drug resistance in the chronic mild stress rat model of depression: a gene expression study. J Mol Neurosci 2007, 33:201-215.
• [24]Schmidt MV, Sterlemann V, Müller MB: Chronic stress and individual vulnerability. Ann N Y Acad Sci 2008, 1148:174-183.
• [25]Li Y, Zheng X, Liang J, Peng Y: Coexistence of anhedonia and anxiety-independent increased novelty-seeking behavior in the chronic mild stress model of depression. Behav Processes 2010, 83:331-339.
• [26]Larsen MH, Mikkelsen JD, Hay-Schmidt A, Sandi C: Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment. J Psychiatr Res 2010, 44:808-16. 2010
• [27]Elizalde, N, Gil-Bea, F, Ramírez, M, Aisa, B, Lasheras, B, Del Rio J, Tordera, R: Long-lasting behavioral effects and recognition memory deficit induced by chronic mild stress in mice: effect of antidepressant treatment. Psychopharm (Berl) 2008, 199:1-14.
• [28]Schweizer M, Henniger M, Sillaber I: Chronic mild stress (CMS) in mice: of anhedonia, 'anomalous anxiolysis' and activity. PLoS One 2009, 4:e4326.
• [29]Michelsen K, van den Hove D, Schmitz C, Segers O, Prickaerts J, Steinbusch H: Prenatal stress and subsequent exposure to chronic mild stress influence dendritic spine density and morphology in the rat medial prefrontal cortex. BMC Neurosci 2007, 8:107. BioMed Central Full Text
• [30]Macrì S, Pasquali P, Bonsignore L, Pieretti S, Cirulli F, Chiarotti F, Laviola G: Moderate neonatal stress decreases within-group variation in behavioral, immune and HPA responses in adult mice. PLoS One 2007, 2:e1015.
• [31]Wood GE, Norris EH, Waters E, Stoldt JT, McEwen BS: Chronic immobilization stress alters aspects of emotionality and associative learning in the rat. Behav Neurosci 2008, 122:282-292.
• [32]Weiss J: Does decreased sucrose intake indicate loss of preference in CMS model? Psychopharm (Berl) 1997, 134:368-377.
• [33]Cabib S: What is mild in mild stress? Psychopharm (Berl) 1997, 134:344-346.
• [34]Harris R, Zhou J, Youngblood B, Smagin G, Ryan D: Failure to change exploration or saccharin preference in rats exposed to chronic mild stress. Physiol Behav 1997, 63:91-100.
• [35]Forbes N, Stewart C, Matthews K, Reid IC: Chronic mild stress and sucrose consumption: validity as a model of depression. Physiol Behav 1996, 60:1481-1484.
• [36]Nielsen C, Arnt J, Sanchez C: Intracranial self-stimulation and sucrose intake differ as hedonic measures following chronic mild stress: interstrain and interindividual differences. Behav Brain Res 2000, 107:21-33.
• [37]Matthews K, Forbes N, Reid I: Sucrose consumption as an hedonic measure following chronic unpredictable mild stress. Physiol Behav 1995, 57:241-248.
• [38]Strekalova T, Steinbusch H: Measuring behavior with chronic stress depression model in mice. Prog Neuropsychopharm Biol Psychiatry 2010, 34:348-361.
• [39]Strekalova T, Steinbusch H: Factors of reproducibility of stress-induced anhedonia in chronic stress depression models in mice. In Mood and Anxiety related phenotypes in mice: characterization using behavioral tests. Edited by Gould T. Totowa, NJ, Humana Press; 2009:153-176.
• [40]Nestler E, Gould E, Manji H, Buncan M, Duman R, Greshenfeld H, Hen R, Kester S, Ledehendleer I, Meaney M, Robbins T, Winsky L, Zalcman S: Preclinical models: Status of basic research in depression. Biol Psychiatry 2002, 52:503-528.
• [41]Ducottet C, Aubert A, Belzung C: Susceptibility to subchronic unpredictable stress is related to individual reactivity to threat stimuli in mice. Behav Brain Res 2004, 155:291-296.
• [42]Strekalova T: The characteristics of the defensive behavior of rats in accordance with their resistance to emotional stress. Zh Vyssh Nerv Deiat Im I P Pavlova 1995, 45:420-422.
• [43]Ivannikova NO, Koplik EV, Popova EN, Sudakov KV: Emotional stress in the development of experimental hemorrhagic stroke in rats with different levels of stress resistance. Neurosci Behav Physiol 2011, 41:35-41.
• [44]Strekalova T, Spanagel R, Bartsch D, Henn F, Gass P: Stressed-induced anhedonia in mice is associated with deficits in forced swimming and exploration. Neuropsychopharm 2004, 11:2007-2017.
• [45]Strekalova T, Gorenkova N, Schunk E, Dolgov O, Bartsch D: Selective effects of citalopram in the mouse model of stress-induced anhedonia with control effects for chronic stress. Behav Pharm 2006, 17:271-287.
• [46]Strekalova T, Cespuglio R, Koval'zon V: Depressive-like state and sleep in laboratory mice. Zh Vyssh Nerv Deiat Im IP Pavlova 2008, 58:728-737.
• [47]Strekalova T: Optimization of the chronic stress depression model in C57 BL/6 mice: evidences for improved validity. In Behavioral models in stress research. Volume I. Edited by Kalueff A, LaPorte J. New York, Nova Science Publishers Inc.; 2008:111-157.
• [48]Strekalova T, Cespuglio R, Kovalson V: Sleep structure during chronic stress and anhedonia in the mouse model of depression. In Behavioral models in stress research. Volume II. NY, USA, Nova Science Publishers; 2009:113-129.
• [49]Strekalova T, van Miegem V, Redkozubova O, Dolgov O, Larde G, Beznosko B, Vankin G, Bachurin S: Sucrose test method: Facts, artifacts and application in anhedonia models with young and old C57BL/6 mice. Int J Nuropsychopharm 2008, 11(Suppl 1):128.
• [50]Cao JL, Covington HE, Friedman AK, Wilkinson MB, Walsh JJ, Cooper DC, Nestler EJ, Han MH: Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action. J Neurosci 2010, 48:16453-16458.
• [51]Covington HE, obo MK, Maze I, Vialou V, Hyman JM, Zaman S, LaPlant Q, Mouzon E, Ghose S, Tamminga CA, Neve RL, Deisseroth K, Nestler EJ: Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J Neurosci 2010, 48:16082-16090.
• [52]Berton O, Covington HE, Ebner K, Tsankova NM, Carle TL, Ulery P, Bhonsle A, Barrot M, Krishnan V, Singewald GM, Singewald N, Birnbaum S, Neve RL, Nestler EJ: Induction of deltaFosB in the periaqueductal gray by stress promotes active coping responses. Neuron 2007, 55:289-300.
• [53]Vialou V, Robison AJ, Laplant QC, Covington HE, Dietz DM, Ohnishi YN, Mouzon E, Rush AJ, Watts EL, Wallace DL, Iñiguez SD, Ohnishi YH, Steiner MA, Warren BL, Krishnan V, Bolaños CA, Neve RL, Ghose S, Berton O, Tamminga CA, Nestler EJ: DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses. Nat Neurosci 2010, 13:745-752.
• [54]Bisgaard CF, Jayatissa MN, Enghild JJ, Sanchéz C, Artemychyn R, Wiborg O: Proteomic investigation of the ventral rat hippocampus links DRP-2 to escitalopram treatment resistance and SNAP to stress resilience in the chronic mild stress model of depression. J Mol Neurosci 2007 32:132-144.
• [55]Holm MM, Nieto-Gonzalez JL, Vardya I, Henningsen K, Jayatissa MN, Wiborg O, Jensen K: Hippocampal GABAergic dysfunction in a rat chronic mild stress model of depression. Hippocampus 2010, in press.
• [56]Henningsen K, Andreasen JT, Bouzinova EV, Jayatissa MN, Jensen MS, Redrobe JP, Wiborg O: Cognitive deficits in the rat chronic mild stress model for depression: relation to anhedonic-like responses. Behav Brain Res 2009, 198:136-141.
• [57]Schmidt MV, Trümbach D, Weber P, Wagner K, Scharf SH, Liebl C, Datson N, Namendorf C, Gerlach T, Kühne C, Uhr M, Deussing JM, Wurst W, Binder EB, Holsboer F, Müller MB: Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus. J Neurosci 2010, 50:16949-16958.
• [58]Lagace DC, Donovan MH, DeCarolis NA, Farnbauch LA, Malhotra S, Berton O, Nestler EJ, Krishnan V, Eisch AJ: Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance. Proc Natl Acad Sci USA 2010, 107:4436-4441.
• [59]Piazza PV, Maccari S, Deminière JM, Le Moal M, Mormède P, Simon H: Corticosterone levels determine individual vulnerability to amphetamine self-administration. Proc Natl Acad Sci USA 1991, 88:2088-2092.
• [60]Ducottet C, Belzung C: Correlations between behaviours in the elevated plus-maze and sensitivity to unpredictable subchronic mild stress: evidence from inbred strains of mice. Behav Brain Res 2005, 156:153-162.
• [61]Le Pen G, Gaudet L, Mortas P, Mory R, Moreau J: Deficits in reward sensitivity in a neurodevelopmental rat model of schizophrenia. Psychopharm (Berl) 2002, 161:434-441.
• [62]Bolivar V, Walters S, Phoenix J: Assessing autism-like behavior in mice: variations in social interactions among inbred strains. Behav Brain Res 2007, 176:2126.
• [63]Jakovcevski M, Schachner M, Morellini F: Individual variability in the stress response of C57BL/6J male mice correlates with trait anxiety. Genes Brain Behav 2008, 2:35-43.
• [64]Ryan BC, Vandenbergh JG: Intrauterine position effects. Neurosci Biobehav Rev 2002, 26:665-678.
• [65]Tsankova N, Berton O, Renthal W, Kumar A, Neve R, Nestler E: Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nature Neurosci 2006, 4:519-525.
• [66]Mill J, Petronis A: Molecular studies of major depressive disorder: the epigenetic perspective. Mol Psychiatry 2007, 12:799-814.
• [67]Rando O, Verstrepen K: Time scales of genetic and epigenetic inheritance. Cell 2007, 128:655-658.
• [68]Alter M, Rubin D, Ramsey K, Halpern R, Stephan D, Abbott L: Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior. PLoS ONE 2008, 3:e3344.
• [69]Prows D, Shertzer H, Daly M, Sidman C, Leikauf G: Genetic analysis of ozone-induced acute lung injury in sensitive and resistant strains of mice. Nature Gen 1997, 17:471-474.
• [70]Ponimaskin E, Dityateva G, Ruonala M, Fukata M, Fukata Y, Kobe F, Dityatev A: Fibroblast growth factor-regulated palmitoylation of the neural cell adhesion molecule determines neuronal morphogenesis. J Neurosci 2008, 28:8897-8907.
• [71]Strekalova T, Wotjak C, Schachner M: Intrahippocampal administration of an antibody against the HNK-1 carbohydrate impairs memory consolidation in an inhibitory learning task in mice. Mol Cell Neurosci 2001, 17:1102-1113.
• [72]Julie Vignisse, Harry SteinbuschWM, Alexei Bolkunov, Joao Nunes, Ana Isabel Santos, Christian Grandfils, Sergei Bachurin, Tatyana Strekalova: Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice. Progr Neuro-Psychopharm Biol Psych 2011, 35:510-522.
• [73]Artola A, von Frijtag JC, Fermont PC, Gispen WH, Schrama LH, Kamal A, Spruijt BM: Long-lasting modulation of the induction of LTD and LTP in rat hippocampal CA1 by behavioural stress and environmental enrichment. Eur J Neurosci 2006, 261-272.
• [74]Popoli M, Gennarelli M, Racagni G: Modulation of synaptic plasticity by stress and antidepressants. Bipolar Disord 2002, 4:166182.
• [75]Lesch KP: When the Serotonin Transporter Gene Meets Adversity: The Contribution of Animal Models to Understanding Epigenetic Mechanisms in Affective Disorders and Resilience. Curr Top Behav Neurosci 2011, in press.
• [76]Dantzer R, O'Connor JC, Lawson MA, Kelley KW: Inflammation-associated depression: From serotonin to kynurenine. Psychoneuroendocrinol 2010, 36:426-436.
• [77]Deacon R: Burrowing in rodents: a sensitive method for detecting behavioral dysfunction. Nature Prot 2006, 1:118-121.
• [78]Freeman M, Freeman S, McElroy S: The comorbidity of bipolar and anxiety disorders: prevalence, psychobiology, and treatment issues. J Affect Disord 2002, 68:1-23.
• [79]Nutt D, Ballenger J, Sheehan D, Wittchen H: Generalized anxiety disorder: comorbidity, comparative biology and treatment. Int J Neuropsychopharmacol 2002, 5:315-325.
• [80]Rao U, Chen LA, Bidesi AS: Hippocampal changes associated with early-life adversity and vulnerability to depression. Biol Psychiatry 2010, 67:357-364.
• [81]Milne A, MacQueen GM, Yucel K: Hippocampal metabolic abnormalities at first onset and with recurrent episodes of a major depressive disorder: a proton magnetic resonance spectroscopy study. Neuroimage 2009, 47:36-41.
• [82]Campbell SJ, Deacon RM, Jiang Y, Ferrari C, Pitossi FJ, Anthony DC: Overexpression of IL-1beta by adenoviral-mediated gene transfer in the rat brain causes a prolonged hepatic chemokine response, axonal injury and the suppression of spontaneous behaviour. Neurobiol Dis 2007, 2:151-163.
• [83]Chung ES, Chung YC, Bok E, Baik HH, Park ES, Park JY, Yoon SH, Jin BK: Fluoxetine prevents LPS-induced degeneration of nigral dopaminergic neurons by inhibiting microglia-mediated oxidative stress. Brain Res 2010, 1363:143-150.
• [84]Maes M: Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuropsychopharmacol Biol Psychiatry 2010, 35:664-675.
• [85]Tonissaar M, Herm L, Rinken A, Harro J: Individual differences in sucrose intake and preference in the rat: circadian variation and association with dopamine D2 receptor function in striatum and nucleus accumbens. Neurosci Lett 2006, 403:119-124.
• [86]Bevins R, Besheer J: Novelty reward as a measure of anhedonia. Neurosci Biobehav Rev 2005, 29:707-714.
• [87]Slattery D, Markou A, Cryan J: Evaluation of reward processes in an animal model of depression. Psychopharm (Berl) 2007, 190:555-568.
• [88]Glendinning J, Gresack J, Spector A: A high-throughput screening procedure for identifying mice with aberrant taste and oromotor function. Chem Senses 2002, 27:461-474.
• [89]Coudereau J, Stain F, Drion N, Sandouk P, Monier C, Debray M, Scherrmann JM, Bourre J, Frances H: Effect of social isolation on the metabolism of morphine and its passage through the blood-brain barrier and on consumption of sucrose solutions. Psychopharm (Berl) 1999, 144:198-204.
• [90]O'Callaghan M, Croft A, Little H: Effects of intraperitoneal injections of saline on the alcohol and sucrose consumption of C57/BL10 mice. Psychopharm (Berl) 2002, 160:206-212.
• [91]Krimm R, Nejad M, Smith J, Miller I Jr, Beidler L: The effect of bilateral sectioning of the chorda tympani and the greater superficial petrosal nerves on the sweet taste in the rat. Physiol Behav 1987, 41:495-501.
• [92]Adriani W, Macri S, Pacifici R, Laviola G: Restricted daily access to water and voluntary nicotine oral consumption in mice: methodological issues and individual differences. Behav Brain Res 2002, 134:21-30.
• [93]Amico J, Vollmer R, Cai H, Miedlar J, Rinaman L: Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion. Am J Physiol Regul Integr Comp Physiol 2005, 289:R1798-806.
• [94]Heyman SE: How mice cope with stressful social situations. Cell 2007, 131:232-234.
• [95]Vachova H: Chronic stress depression model in mice. Social characteristics in mice and their physiological correlates: two studies. Diploma work at the department of zoology, Charle's University in Prague 2004, 2-32.
• [96]Willner P, D'Aquila P, Coventry T, Brain P: Loss of social status: preliminary evaluation of a novel animal model of depression. J Psychopharmacol 1995, 9:207-213.
• [97]D'Amato F, Rizzi R, Moles A: A model of social stress in non-submissive mice: effects on sociosexual behaviour. Physiol Behav 2001, 73:421-426.
• [98]Von Frijtag J, Reijmers L, Van der Harst J, Leus I, Van den Bos R, Spruijt B: Defeat followed by individual housing results in long-term impaired reward- and cognition-related behaviours in rats. Behav Brain Res 2000, 117:137146.
• [99]Malatynska E, Knapp R: Dominant-submissive behavior as models of mania and depression. Neurosci Biobehav Rev 2005, 29:715-737.
• [100]Krishnan V, Nestler EJ: Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry 2010, 167:1305-1320.
• [101]Krsiak M: Timid singly-housed mice: their value in prediction of psychotropic activity of drugs. Br J Pharmacol 1975, 55:141-150.
• [102]Krsiak M, Podhorna J, Miczek K: Aggressive and social behavior after alprazolam withdrawal: experimental therapy with Ro 19-8022. Neurosci Biobehav Rev 1998, 23:155-161.
• [103]Hata T, Itoh E, Nishikawa H: Behavioral characteristics of SART-stressed mice in the forced swim test and drug action. Pharmacol Biochem Behav 1995, 51:849-853.
• [104]Hata T, Nishikawa H, Itoh E, Funakami Y: Anxiety-like behavior in elevated plus-maze in repeatedly cold stressed mice. Jpn J Pharmacol 2001, 85:189-196.
• [105]Cancela L, Bregonzio C, Molina V: Anxiolytic-like effect induced by chronic stress is reversed by naloxone pretreatment. Brain Res Bull 1995, 36:209-213.
• [106]D'Aquila P, Brain P, Willner P: Effects of chronic mild stress on performance in behavioural tests relevant to anxiety and depression. Physiol Behav 1994, 56:861-867.
• [107]Rossler A, Joubert C, Chapouthier G: Chronic mild stress alleviates anxious behaviour in female mice in two situations. Behav Processes 2000, 49:163-165.
• [108]Strekalova T, Spanagel R, Dolgov O, Bartsch D: Stress-induced hyperlocomotion as a confounding factor in anxiety and depression models in mice. Behav Pharm 2005, 16:171-180.
• [109]Cao L, Hudson C, Moynihan J: Chronic foot shock induces hyperactive behaviors and accompanying pro- and anti-inflammatory responses in mice. J Neuroimmunol 2007, 186:63-74.
• [110]Wakizono T, Sawamura T, Shimizu K, Nibuya M, Suzuki G, Toda H, Hirano J, Kikuchi A, Takahashi Y, Nomura S: Stress vulnerabilities in an animal model of post-traumatic stress disorder. Physiol Behav 2007, 90:687-695.
• [111]Becker C, Zeau B, Rivat C, Blugeot A, Hamon M, Benoliel J: Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin. Mol Psychiatry 2008, 13:1079-92.
• [112]Sanchez C: Acute stress enhances anxiolytic-like drug responses of mice tested in a black and white test box. Eur Neuropsychopharm 1997, 7:283-238.
• [113]Heiderstadt K, McLaughlin R, Wright D, Walker S, Gomez-Sanchez C: The effect of chronic food and water restriction on open-field behavior and serum corticosterone levels in rats. Lab Anim 2000, 34:20-28.
• [114]Burne T, O'Loan J, McGrath J, Eyles D: Hyperlocomotion associated with transient prenatal vitamin D deficiency is ameliorated by acute restraint. Behav Brain Res 2006, 174:119-124.
• [115]Negroni J, Venault P, Pardon M, Perez-Diaz F, Chapouthier G, Cohen-Salmon C: Chronic ultra-mild stress improves locomotor performance of B6D2F1 mice in a motor risk situation. Behav Brain Res 2004, 155:65-73.
• [116]Bertoglio L, Carobrez A: Behavioral profile of rats submitted to session 1-session 2 in the elevated plus-maze during diurnal/nocturnal phases and under different illumination conditions. Behav Brain Res 2002, 132:135-113.
• [117]Igarashi E, Takeshita S: Effects of illumination and handling upon rat open field activity. Physiol Behav 1995, 57:699-703.
• [118]Valentinuzzi V, Buxton O, Chang A, Scarbrough K, Ferrari E, Takahashi J, Turek F: Locomotor response to an open field during C57BL/6J active and inactive phases: differences dependent on conditions of illumination. Physiol Behav 2000, 69:269-275.
• [119]Murison R, Hansen A: Reliability of the chronic mild stress paradigm: implications for research and animal welfare. Integr Physiol Behav Sci 2001, 36:266-274.
• [120]Pijlman F, Wolterink G, Van Ree J: Physical and emotional stress has differential effects on preference for saccharine and open field behaviour in rats. Behav Brain Res 2003, 139:131-138.
• [121]Ikemoto S, Panksepp J: The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking. Brain Res Brain Res Rev 1999, 1:6-41.
• [122]Crawley J, Moody T: Anxiolytics block excessive grooming behavior induced by ACTH1-24 and bombesin. Brain Res Bull 1983, 10:399-401.
• [123]Skuse D, Albanese A, Stanhope R, Gilmour J, Voss L: New stress-related syndrome of growth failure and hyperphagia in children, associated with reversibility of growth-hormone insufficiency. Lancet 1996, 348:353-358.
• [124]Schoenecker B, Heller K, Freimanis T: Development of stereotypies and polydipsia in wild caught bank voles (Clethrionomys glareolus) and their laboratory-bred offspring. Is polydipsia a symptom of diabetes mellitus? Appl Anim Behav Sci 2000, 68:349-357.
• [125]Cole B, Koob G: Corticotropin-releasing factor and schedule-induced polydipsia. Pharmacol Biochem Behav 1994, 47:393-398.
• [126]Yirmiya R, Goshen I, Bajayo A, Kreisel T, Feldman S, Tam J, Trembovler V, Csernus V, Shohami E, Bab I: Depression induces bone loss through stimulation of the sympathetic nervous system. Proc Natl Acad Sci USA 2006, 45:16876-168781.
• [127]Mendlewicz J: Sleep disturbances: core symptoms of major depressive disorder rather than associated or comorbid disorders. World J Biol Psychiatry 2009, 10:269-275.
• [128]Wilkinson M, Xiao G, Kumar A, LaPlant Q, Renthal W, Sikder D, Kodadek T, Nestler E: Imipramine treatment and resiliency exhibit similar chromatin regulation in the mouse nucleus accumbens in depression models. J Neurosci 2009, 29:7820-7832.
• [129]Perlis R, Moorjani P, Fagerness J, Purcell S, Trivedi M, Fava M, Rush A, Smoller J: Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study. Neuropsychopharm 2008, 33:2810-2819.
• [130]Maina G, Albert U, Salvi V, Bogetto F: Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. J Clin Psychiatry 2004, 65:1365-1371.
• [131]Hayward C, Wilson K, Lagle K, Kraemer H, Killen J, Taylor C: The developmental psychopathology of social anxiety in adolescents. Depress Anxiety 2008, 25:200-206.
• [132]Stahl S: Phenomenology of anxiety disorders: clinical heterogeneity and comorbidity. In Advances in the Neurobiology of Anxiety Disorders. Edited by Westenberg H, Den Boer J, Murphy D. John Willey & Sons; 1996:21-38.