Skip to main content
SpringerLink
Log in

Towards translational rodent models of depression

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Rodent models of depression have been developed in an effort to identify novel antidepressant compounds and to further our understanding of the pathophysiology of depression. Various rodent models of depression and antidepressant-like behaviour are currently used but, clearly, none of these current models fully recapitulate all features of depression. Moreover, these models have not resulted in the development of novel non-monoaminergic-based antidepressants with clinical efficacy. Thus, a refinement of the current models of depression is required. The present review outlines the most commonly used models of depression and antidepressant drug-like activity and suggests several factors that should be considered when refining these models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Abe H, Hidaka N, Kawagoe C, Odagiri K, Watanabe Y, Ikeda T, Ishizuka Y, Hashiguchi H, Takeda R, Nishimori T, Ishida Y (2007) Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis. Neurosci Res 59:145–151

    Article  PubMed  CAS  Google Scholar 

  • Airan RD, Meltzer LA, Roy M, Gong Y, Chen H, Deisseroth K (2007) High-speed imaging reveals neurophysiological links to behavior in an animal model of depression. Science 317:819–823

    Article  PubMed  CAS  Google Scholar 

  • American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders IV (DSM-IV). American Psychiatric Association, Arlington

    Google Scholar 

  • Anderson MH, Hardcastle C, Munafo MR, Robinson ES (2012) Evaluation of a novel translational task for assessing emotional biases in different species. Cogn Affect Behav Neurosci 12:373–381

    Article  PubMed  Google Scholar 

  • Anisman H, Matheson K (2005) Stress, depression, and anhedonia: caveats concerning animal models. Neurosci Biobehav Rev 29:525–546

    Article  PubMed  Google Scholar 

  • Anisman H, Merali Z, Hayley S (2008) Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: comorbidity between depression and neurodegenerative disorders. Prog Neurobiol 85:1–74

    Article  PubMed  CAS  Google Scholar 

  • Arango V, Underwood MD, Mann JJ (2002) Serotonin brain circuits involved in major depression and suicide. Prog Brain Res 136:443–453

    Article  PubMed  CAS  Google Scholar 

  • Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91–95

    Article  PubMed  CAS  Google Scholar 

  • Bale TL (2006) Stress sensitivity and the development of affective disorders. Horm Behav 50:529–533

    Article  PubMed  CAS  Google Scholar 

  • Bangasser DA, Curtis A, Reyes BA, Bethea TT, Parastatidis I, Ischiropoulos H, Van Bockstaele EJ, Valentino RJ (2010) Sex differences in corticotropin-releasing factor receptor signaling and trafficking: potential role in female vulnerability to stress-related psychopathology. Mol Psychiatry 15:896–904

    Article  CAS  Google Scholar 

  • Barr AM, Markou A (2005) Psychostimulant withdrawal as an inducing condition in animal models of depression. Neurosci Biobehav Rev 29:675–706

    Article  PubMed  CAS  Google Scholar 

  • Barr AM, Phillips AG (1999) Withdrawal following repeated exposure to d-amphetamine decreases responding for a sucrose solution as measured by a progressive ratio schedule of reinforcement. Psychopharmacology (Berl) 141:99–106

    Article  CAS  Google Scholar 

  • Barr AM, Fiorino DF, Phillips AG (1999) Effects of withdrawal from an escalating dose schedule of d-amphetamine on sexual behavior in the male rat. Pharmacol Biochem Behav 64:597–604

    Article  PubMed  CAS  Google Scholar 

  • Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354

    Article  PubMed  CAS  Google Scholar 

  • Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868

    Article  PubMed  CAS  Google Scholar 

  • Berton O, Hahn CG, Thase ME (2012) Are we getting closer to valid translational models for major depression? Science 338:75–79

    Article  PubMed  CAS  Google Scholar 

  • Beurel E, Song L, Jope RS (2011) Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice. Mol Psychiatry 16:1068–1070

    Article  PubMed  CAS  Google Scholar 

  • Bisgaard CF, Jayatissa MN, Enghild JJ, Sanchez C, Artemychyn R, Wiborg O (2007) 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 32:132–144

    Article  PubMed  CAS  Google Scholar 

  • Bisgaard CF, Bak S, Christensen T, Jensen ON, Enghild JJ, Wiborg O (2012) Vesicular signalling and immune modulation as hedonic fingerprints: proteomic profiling in the chronic mild stress depression model. J Psychopharmacol 26:1569–1583

    Article  PubMed  Google Scholar 

  • Bondi CO, Rodriguez G, Gould GG, Frazer A, Morilak DA (2008) Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology 33:320–331

    Article  PubMed  CAS  Google Scholar 

  • Brigman JL, Mathur P, Harvey-White J, Izquierdo A, Saksida LM, Bussey TJ, Fox S, Deneris E, Murphy DL, Holmes A (2010) Pharmacological or genetic inactivation of the serotonin transporter improves reversal learning in mice. Cereb Cortex 20:1955–1963

    Article  PubMed  Google Scholar 

  • Bussey TJ, Holmes A, Lyon L, Mar AC, McAllister KA, Nithianantharajah J, Oomen CA, Saksida LM (2012) New translational assays for preclinical modelling of cognition in schizophrenia: the touchscreen testing method for mice and rats. Neuropharmacology 62:1191–1203

    Article  PubMed  CAS  Google Scholar 

  • Carola V, Gross C (2012) Mouse models of the 5-HTTLPR × stress risk factor for depression. Curr Top Behav Neurosci 12:59–72

    Article  PubMed  Google Scholar 

  • Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389

    Article  PubMed  CAS  Google Scholar 

  • Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW, Ferguson D, Tsai HC, Pomeranz L, Christoffel DJ, Nectow AR, Ekstrand M, Domingos A, Mazei-Robison MS, Mouzon E, Lobo MK, Neve RL, Friedman JM, Russo SJ, Deisseroth K, Nestler EJ, Han MH (2013) Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493:532–536

    Article  PubMed  CAS  Google Scholar 

  • Chourbaji S, Zacher C, Sanchis-Segura C, Dormann C, Vollmayr B, Gass P (2005) Learned helplessness: validity and reliability of depressive-like states in mice. Brain Res Brain Res Protocol 16:70–78

    Article  CAS  Google Scholar 

  • Chourbaji S, Pfeiffer N, Dormann C, Brandwein C, Fradley R, Sheardown M, Gass P (2010) The suitability of 129SvEv mice for studying depressive-like behaviour: both males and females develop learned helplessness. Behav Brain Res 211:105–110

    Article  PubMed  Google Scholar 

  • Christensen T, Bisgaard CF, Wiborg O (2011) Biomarkers of anhedonic-like behavior, antidepressant drug refraction, and stress resilience in a rat model of depression. Neuroscience 196:66–79

    Article  PubMed  CAS  Google Scholar 

  • Covington HE 3rd, Lobo MK, Maze I, Vialou V, Hyman JM, Zaman S, LaPlant Q, Mouzon E, Ghose S, Tamminga CA, Neve RL, Deisseroth K, Nestler EJ (2010) Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J Neurosci 30:16082–16090

    Article  PubMed  CAS  Google Scholar 

  • Crowley JJ, Lucki I (2005) Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics. Curr Pharm Des 11:157–169

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Mombereau C (2004) In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 9:326–357

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, O’Leary OF (2010) Neuroscience. A glutamate pathway to faster-acting antidepressants? Science 329:913–914

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Slattery DA (2007) Animal models of mood disorders: recent developments. Curr Opin Psychiatry 20:1–7

    Article  PubMed  Google Scholar 

  • Cryan JF, Hoyer D, Markou A (2003) Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents. Biol Psychiatry 54:49–58

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, O’Leary OF, Jin SH, Friedland JC, Ouyang M, Hirsch BR, Page ME, Dalvi A, Thomas SA, Lucki I (2004) Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors. Proc Natl Acad Sci USA 101:8186–8191

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Valentino RJ, Lucki I (2005) Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav Rev 29:547–569

    Article  PubMed  CAS  Google Scholar 

  • Dalla C, Pitychoutis PM, Kokras N, Papadopoulou-Daifoti Z (2011) Sex differences in response to stress and expression of depressive-like behaviours in the rat. Curr Top Behav Neurosci 8:97–118

    Article  PubMed  CAS  Google Scholar 

  • DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, Henter ID, Luckenbaugh DA, Machado-Vieira R, Zarate CA Jr (2010) Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry 71:1605–1611

    Article  PubMed  CAS  Google Scholar 

  • Disner SG, Beevers CG, Haigh EA, Beck AT (2011) Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci 12:467–477

    Article  PubMed  CAS  Google Scholar 

  • Ducottet C, Griebel G, Belzung C (2003) Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist antalarmin in the chronic mild stress model of depression in mice. Prog Neuropsychopharmacol Biol Psychiatry 27:625–631

    Article  PubMed  CAS  Google Scholar 

  • Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127

    Article  PubMed  CAS  Google Scholar 

  • Duman RS, Li N, Liu RJ, Duric V, Aghajanian G (2012) Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology 62:35–41

    Article  PubMed  CAS  Google Scholar 

  • El Yacoubi M, Vaugeois JM (2007) Genetic rodent models of depression. Curr Opin Pharmacol 7:3–7

    Article  PubMed  CAS  Google Scholar 

  • El Yacoubi M, Bouali S, Popa D, Naudon L, Leroux-Nicollet I, Hamon M, Costentin J, Adrien J, Vaugeois JM (2003) Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression. Proc Natl Acad Sci USA 100:6227–6232

    Article  PubMed  CAS  Google Scholar 

  • Enkel T, Gholizadeh D, Bohlen und Halbach O von, Sanchis-Segura C, Hurlemann R, Spanagel R, Gass P, Vollmayr B (2010) Ambiguous-cue interpretation is biased under stress- and depression-like states in rats. Neuropsychopharmacology 35:1008–1015

    Google Scholar 

  • Fan M, Liu B, Jiang T, Jiang X, Zhao H, Zhang J (2010) Meta-analysis of the association between the monoamine oxidase-A gene and mood disorders. Psychiatr Genet 20:1–7

    Article  PubMed  CAS  Google Scholar 

  • Finger BC, Dinan TG, Cryan JF (2011) High-fat diet selectively protects against the effects of chronic social stress in the mouse. Neuroscience 192:351–360

    Article  PubMed  CAS  Google Scholar 

  • Forbes NF, Stewart CA, Matthews K, Reid IC (1996) Chronic mild stress and sucrose consumption: validity as a model of depression. Physiol Behav 60:1481–1484

    Article  PubMed  CAS  Google Scholar 

  • Franklin TB, Russig H, Weiss IC, Graff J, Linder N, Michalon A, Vizi S, Mansuy IM (2010) Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry 68:408–415

    Article  PubMed  Google Scholar 

  • Frasure-Smith N, Lesperance F, Talajic M (1995) Depression and 18-month prognosis after myocardial infarction. Circulation 91:999–1005

    Article  PubMed  CAS  Google Scholar 

  • Frye CA, Edinger KL, Lephart ED, Walf AA (2010) 3Alpha-androstanediol, but not testosterone, attenuates age-related decrements in cognitive, anxiety, and depressive behavior of male rats. Front Aging Neurosci 2:15

    PubMed  CAS  Google Scholar 

  • Gass P, Reichardt HM, Strekalova T, Henn F, Tronche F (2001) Mice with targeted mutations of glucocorticoid and mineralocorticoid receptors: models for depression and anxiety? Physiol Behav 73:811–825

    Article  PubMed  CAS  Google Scholar 

  • Geller B, Cooper TB, McCombs HG, Graham D, Wells J (1989) Double-blind, placebo-controlled study of nortriptyline in depressed children using a “fixed plasma level” design. Psychopharmacol Bull 25:101–108

    PubMed  CAS  Google Scholar 

  • Geller B, Cooper TB, Graham DL, Marsteller FA, Bryant DM (1990) Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a “fixed plasma level” design. Psychopharmacol Bull 26:85–90

    PubMed  CAS  Google Scholar 

  • Gerritsen L, Comijs HC, Graaf Y van der, Knoops AJ, Penninx BW, Geerlings MI (2011) Depression, hypothalamic pituitary adrenal axis, and hippocampal and entorhinal cortex volumes—the SMART Medea study. Biol Psychiatry 70:373–380

    Google Scholar 

  • Geyer MA, Markou A (1995) Animal models of psychiatric disorders. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology—the 4th generation of progress. Raven, New York, pp 787–798

    Google Scholar 

  • Godbout JP, Moreau M, Lestage J, Chen J, Sparkman NL, O’Connor J, Castanon N, Kelley KW, Dantzer R, Johnson RW (2008) Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology 33:2341–2351

    Article  PubMed  CAS  Google Scholar 

  • Goel N, Bale TL (2009) Examining the intersection of sex and stress in modelling neuropsychiatric disorders. J Neuroendocrinol 21:415–420

    Article  PubMed  CAS  Google Scholar 

  • Goodman WK, Murphy TK, Storch EA (2007) Risk of adverse behavioral effects with pediatric use of antidepressants. Psychopharmacology (Berl) 191:87–96

    Article  CAS  Google Scholar 

  • Graybeal C, Feyder M, Schulman E, Saksida LM, Bussey TJ, Brigman JL, Holmes A (2011) Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF. Nat Neurosci 14:1507–1509

    Article  PubMed  CAS  Google Scholar 

  • Haller J, Fuchs E, Halasz J, Makara GB (1999) Defeat is a major stressor in males while social instability is stressful mainly in females: towards the development of a social stress model in female rats. Brain Res Bull 50:33–39

    Article  PubMed  CAS  Google Scholar 

  • Hamani C, Diwan M, Macedo CE, Brandao ML, Shumake J, Gonzalez-Lima F, Raymond R, Lozano AM, Fletcher PJ, Nobrega JN (2010) Antidepressant-like effects of medial prefrontal cortex deep brain stimulation in rats. Biol Psychiatry 67:117–124

    Article  PubMed  Google Scholar 

  • Hammack SE, Richey KJ, Schmid MJ, LoPresti ML, Watkins LR, Maier SF (2002) The role of corticotropin-releasing hormone in the dorsal raphe nucleus in mediating the behavioral consequences of uncontrollable stress. J Neurosci 22:1020–1026

    PubMed  CAS  Google Scholar 

  • Hansen HH, Sanchez C, Meier E (1997) Neonatal administration of the selective serotonin reuptake inhibitor Lu 10-134-C increases forced swimming-induced immobility in adult rats: a putative animal model of depression? J Pharmacol Exp Ther 283:1333–1341

    PubMed  CAS  Google Scholar 

  • Harding EJ, Paul ES, Mendl M (2004) Animal behaviour: cognitive bias and affective state. Nature 427:312

    Article  PubMed  CAS  Google Scholar 

  • Harvey PD, Reichenberg A, Bowie CR (2006) Cognition and aging in psychopathology: focus on schizophrenia and depression. Annu Rev Clin Psychol 2:389–409

    Article  PubMed  Google Scholar 

  • Hek K, Demirkan A, Lahti J, Terracciano A, Teumer A, Cornelis MC, Amin N, Bakshis E, Baumert J, Ding J, Liu Y, Marciante K, Meirelles O, Nalls MA, Sun YV, Vogelzangs N, Yu L, Bandinelli S, Benjamin EJ, Bennett DA, Boomsma D, Cannas A, Coker LH, Geus E de, De Jager PL, Diez-Roux AV, Purcell S, Hu FB, Rimm EB, Hunter DJ, Jensen MK, Curhan G, Rice K, Penman AD, Rotter JI, Sotoodehnia N, Emeny R, Eriksson JG, Evans DA, Ferrucci L, Fornage M, Gudnason V, Hofman A, Illig T, Kardia S, Kelly-Hayes M, Koenen K, Kraft P, Kuningas M, Massaro JM, Melzer D, Mulas A, Mulder CL, Murray A, Oostra BA, Palotie A, Penninx B, Petersmann A, Pilling LC, Psaty B, Rawal R, Reiman EM, Schulz A, Shulman JM, Singleton AB, Smith AV, Sutin AR, Uitterlinden AG, Volzke H, Widen E, Yaffe K, Zonderman AB, Cucca F, Harris T, Ladwig KH, Llewellyn DJ, Raikkonen K, Tanaka T, Duijn CM van, Grabe HJ, Launer LJ, Lunetta KL, Mosley TH Jr, Newman AB, Tiemeier H, Murabito J (2013) A genome-wide association study of depressive symptoms. Biol Psychiatry 73(7):667–678. doi:10.1016/j.biopsych.2012.09.033

  • Hellweg R, Zueger M, Fink K, Hortnagl H, Gass P (2007) Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression-related brain areas. Neurobiol Dis 25:1–7

    Article  PubMed  CAS  Google Scholar 

  • Hendrie C, Pickles A (2012) The failure of the antidepressant drug discovery process is systemic. J Psychopharmacol. doi:10.1177/0269881112466185

  • Henn FA, Vollmayr B (2005) Stress models of depression: forming genetically vulnerable strains. Neurosci Biobehav Rev 29:799–804

    Article  PubMed  Google Scholar 

  • Herzog CJ, Czeh B, Corbach S, Wuttke W, Schulte-Herbruggen O, Hellweg R, Flugge G, Fuchs E (2009) Chronic social instability stress in female rats: a potential animal model for female depression. Neuroscience 159:982–992

    Article  PubMed  CAS  Google Scholar 

  • Hughes V (2012) Stress: the roots of resilience. Nature 490:165–167

    Article  PubMed  CAS  Google Scholar 

  • Inta D, Trusel M, Riva MA, Sprengel R, Gass P (2009) Differential c-Fos induction by different NMDA receptor antagonists with antidepressant efficacy: potential clinical implications. Int J Neuropsychopharmacol 12:1133–1136

    Article  PubMed  CAS  Google Scholar 

  • Iwata M, Ota KT, Duman RS (2012) The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun. doi:10.1016/j.bbi.2012.12.008

  • Jacobson LH, Cryan JF (2007) Feeling strained? Influence of genetic background on depression-related behavior in mice: a review. Behav Genet 37:171–213

    Article  PubMed  CAS  Google Scholar 

  • Jayatissa MN, Bisgaard C, Tingstrom A, Papp M, Wiborg O (2006) Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression. Neuropsychopharmacology 31:2395–2404

    Article  PubMed  CAS  Google Scholar 

  • Kales HC, Maixner DF, Mellow AM (2005) Cerebrovascular disease and late-life depression. Am J Geriatr Psychiatry 13:88–98

    PubMed  Google Scholar 

  • Karel MJ (1997) Aging and depression: vulnerability and stress across adulthood. Clin Psychol Rev 17:847–879

    Article  PubMed  CAS  Google Scholar 

  • Kavalali ET, Monteggia LM (2012) Synaptic mechanisms underlying rapid antidepressant action of ketamine. Am J Psychiatry 169:1150–1156

    Article  PubMed  Google Scholar 

  • Kendler KS, Gardner CO (2001) Monozygotic twins discordant for major depression: a preliminary exploration of the role of environmental experiences in the aetiology and course of illness. Psychol Med 31:411–423

    PubMed  CAS  Google Scholar 

  • Kessler RC (1997) The effects of stressful life events on depression. Annu Rev Psychol 48:191–214

    Article  PubMed  CAS  Google Scholar 

  • Kessler RC, McGonagle KA, Swartz M, Blazer DG, Nelson CB (1993) Sex and depression in the national comorbidity survey. I. Lifetime prevalence, chronicity and recurrence. J Affect Disord 29:85–96

    Article  PubMed  CAS  Google Scholar 

  • King JA, Campbell D, Edwards E (1993) Differential development of the stress response in congenital learned helplessness. Int J Dev Neurosci 11:435–442

    Article  PubMed  CAS  Google Scholar 

  • Kitamura Y, Araki H, Gomita Y (2002) Influence of ACTH on the effects of imipramine, desipramine and lithium on duration of immobility of rats in the forced swim test. Pharmacol Biochem Behav 71:63–69

    Article  PubMed  CAS  Google Scholar 

  • Kitamura Y, Akiyama K, Kitagawa K, Shibata K, Kawasaki H, Suemaru K, Araki H, Sendo T, Gomita Y (2008) Chronic coadministration of carbamazepine together with imipramine produces antidepressant-like effects in an ACTH-induced animal model of treatment-resistant depression: involvement of 5-HT(2A) receptors? Pharmacol Biochem Behav 89:235–240

    Article  PubMed  CAS  Google Scholar 

  • Koo JW, Duman RS (2008) IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci USA 105:751–756

    Article  PubMed  CAS  Google Scholar 

  • Kos T, Popik P, Pietraszek M, Schafer D, Danysz W, Dravolina O, Blokhina E, Galankin T, Bespalov AY (2006) Effect of 5-HT3 receptor antagonist MDL 72222 on behaviors induced by ketamine in rats and mice. Eur Neuropsychopharmacol 16:297–310

    Article  PubMed  CAS  Google Scholar 

  • Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E, Hale JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Carlson EJ, Hargreaves RJ, Rupniak NM (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281:1640–1645

    Article  PubMed  CAS  Google Scholar 

  • Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, Laplant Q, Graham A, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green TA, Neve RL, Chakravarty S, Kumar A, Eisch AJ, Self DW, Lee FS, Tamminga CA, Cooper DC, Gershenfeld HK, Nestler EJ (2007) Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131:391–404

    Article  PubMed  CAS  Google Scholar 

  • Kutcher S, Boulos C, Ward B, Marton P, Simeon J, Ferguson HB, Szalai J, Katic M, Roberts N, Dubois C et al (1994) Response to desipramine treatment in adolescent depression: a fixed-dose, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 33:686–694

    Article  PubMed  CAS  Google Scholar 

  • Ladd CO, Owens MJ, Nemeroff CB (1996) Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology 137:1212–1218

    Article  PubMed  CAS  Google Scholar 

  • Lapiz-Bluhm MD, Bondi CO, Doyen J, Rodriguez GA, Bedard-Arana T, Morilak DA (2008) Behavioural assays to model cognitive and affective dimensions of depression and anxiety in rats. J Neuroendocrinol 20:1115–1137

    Article  PubMed  CAS  Google Scholar 

  • Leonard B, Maes M (2012) Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 36:764–785

    Article  PubMed  CAS  Google Scholar 

  • Li B, Suemaru K, Cui R, Kitamura Y, Gomita Y, Araki H (2006) Repeated electroconvulsive stimuli increase brain-derived neurotrophic factor in ACTH-treated rats. Eur J Pharmacol 529:114–121

    Article  PubMed  CAS  Google Scholar 

  • Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959–964

    Article  PubMed  CAS  Google Scholar 

  • Lin D, Bruijnzeel AW, Schmidt P, Markou A (2002) Exposure to chronic mild stress alters thresholds for lateral hypothalamic stimulation reward and subsequent responsiveness to amphetamine. Neuroscience 114:925–933

    Article  PubMed  CAS  Google Scholar 

  • Lindholm JS, Autio H, Vesa L, Antila H, Lindemann L, Hoener MC, Skolnick P, Rantamaki T, Castren E (2012) The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor potentiator LY 451646 are preserved in bdnf(+)/(−) heterozygous null mice. Neuropharmacology 62:391–397

    Article  PubMed  CAS  Google Scholar 

  • Loftis JM, Huckans M, Morasco BJ (2010) Neuroimmune mechanisms of cytokine-induced depression: current theories and novel treatment strategies. Neurobiol Dis 37:519–533

    Article  PubMed  CAS  Google Scholar 

  • Lucki I (1997) The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 8:523–532

    Article  PubMed  CAS  Google Scholar 

  • Lucki I, O’Leary OF (2004) Distinguishing roles for norepinephrine and serotonin in the behavioral effects of antidepressant drugs. J Clin Psychiatry 65 (Suppl 4):11–24

    PubMed  CAS  Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445

    Article  PubMed  CAS  Google Scholar 

  • Maccari S, Morley-Fletcher S (2007) Effects of prenatal restraint stress on the hypothalamus-pituitary-adrenal axis and related behavioural and neurobiological alterations. Psychoneuroendocrinology 32 (Suppl 1):S10–S15

    Article  PubMed  CAS  Google Scholar 

  • Maciag D, Simpson KL, Coppinger D, Lu Y, Wang Y, Lin RC, Paul IA (2006) Neonatal antidepressant exposure has lasting effects on behavior and serotonin circuitry. Neuropsychopharmacology 31:47–57

    PubMed  CAS  Google Scholar 

  • Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, Manji HK (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 63:349–352

    Article  PubMed  CAS  Google Scholar 

  • Malkesman O, Braw Y, Maayan R, Weizman A, Overstreet DH, Shabat-Simon M, Kesner Y, Touati-Werner D, Yadid G, Weller A (2006) Two different putative genetic animal models of childhood depression. Biol Psychiatry 59:17–23

    Article  PubMed  CAS  Google Scholar 

  • Malkesman O, Scattoni ML, Paredes D, Tragon T, Pearson B, Shaltiel G, Chen G, Crawley JN, Manji HK (2010) The female urine sniffing test: a novel approach for assessing reward-seeking behavior in rodents. Biol Psychiatry 67:864–871

    Article  PubMed  CAS  Google Scholar 

  • Markou A, Koob GF (1991) Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacology 4:17–26

    PubMed  CAS  Google Scholar 

  • Matthews K, Forbes N, Reid IC (1995) Sucrose consumption as an hedonic measure following chronic unpredictable mild stress. Physiol Behav 57:241–248

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS (2012) Brain on stress: how the social environment gets under the skin. Proc Natl Acad Sci USA 109 (Suppl 2):17180–17185

    Article  PubMed  CAS  Google Scholar 

  • McKernan DP, Dinan TG, Cryan JF (2009) “Killing the blues”: a role for cellular suicide (apoptosis) in depression and the antidepressant response? Prog Neurobiol 88:246–263

    Article  PubMed  CAS  Google Scholar 

  • Moreau JL (2002) Simulating the anhedonia symptom of depression in animals. Dialogues Clin Neurosci 4:351–360

    PubMed  Google Scholar 

  • Murphy DL, Lesch KP (2008) Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 9:85–96

    Article  PubMed  CAS  Google Scholar 

  • Naudon L, El Yacoubi M, Vaugeois JM, Leroux-Nicollet I, Costentin J (2002) A chronic treatment with fluoxetine decreases 5-HT(1A) receptors labeling in mice selected as a genetic model of helplessness. Brain Res 936:68–75

    Article  PubMed  CAS  Google Scholar 

  • Nelson JC, Mazure CM, Jatlow PI (1995) Desipramine treatment of major depression in patients over 75 years of age. J Clin Psychopharmacol 15:99–105

    Article  PubMed  CAS  Google Scholar 

  • Neumann ID, Wegener G, Homberg JR, Cohen H, Slattery DA, Zohar J, Olivier JD, Mathe AA (2011) Animal models of depression and anxiety: what do they tell us about human condition? Prog Neuropsychopharmacol Biol Psychiatry 35:1357–1375

    Article  PubMed  CAS  Google Scholar 

  • Nielsen CK, Arnt J, Sanchez C (2000) Intracranial self-stimulation and sucrose intake differ as hedonic measures following chronic mild stress: interstrain and interindividual differences. Behav Brain Res 107:21–33

    Article  PubMed  CAS  Google Scholar 

  • Nouwen A, Winkley K, Twisk J, Lloyd CE, Peyrot M, Ismail K, Pouwer F (2010) Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia 53:2480–2486

    Article  PubMed  CAS  Google Scholar 

  • O’Connor RM, Dinan TG, Cryan JF (2011) miRNAS as novel antidepressant targets: converging effects of acute ketamine, electroconvulsive shock therapy and chronic fluoxetine treatments. Behav Pharmacol 22:e70

    Google Scholar 

  • O’Donnell JM, Marek GJ, Seiden LS (2005) Antidepressant effects assessed using behavior maintained under a differential-reinforcement-of-low-rate (DRL) operant schedule. Neurosci Biobehav Rev 29:785–798

    Article  PubMed  CAS  Google Scholar 

  • O’Leary OF, Cryan JF (2009) The tail suspension test: a model for characterizing antidepressant activity in mice. In: Gould T (ed) Mood and anxiety related phenotypes in mice; neuromethods. Springer, Berlin, pp 119–137

    Chapter  Google Scholar 

  • O’Leary OF, Cryan JF (2010) The behavioural genetics of serotonin: relevance to anxiety and depression. In: Muller CP, Jacobs BL (eds) Handbook of the behavioral neurobiology of serotonin. Academic Press, USA, pp 749–791

    Chapter  Google Scholar 

  • O’Leary OF, Zandy S, Dinan TG, Cryan JF (2013) Lithium augmentation of the effects of desipramine in a mouse model of treatment-resistant depression: a role for hippocampal cell proliferation. Neuroscience 228:36–46

    Article  PubMed  CAS  Google Scholar 

  • O’Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EM, Cryan JF, Dinan TG (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65:263–267

    Article  PubMed  Google Scholar 

  • Olivier JD, Van Der Hart MG, Van Swelm RP, Dederen PJ, Homberg JR, Cremers T, Deen PM, Cuppen E, Cools AR, Ellenbroek BA (2008) A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders. Neuroscience 152:573–584

    Article  PubMed  CAS  Google Scholar 

  • Onodera T, Watanabe R, Tha KK, Hayashi Y, Murayama T, Okuma Y, Ono C, Oketani Y, Hosokawa M, Nomura Y (2000) Depressive behavior and alterations in receptors for dopamine and 5-hydroxytryptamine in the brain of the senescence accelerated mouse (SAM)-P10. Jpn J Pharmacol 83:312–318

    Article  PubMed  CAS  Google Scholar 

  • Overstreet DH, Wegener G (2013) The Flinders sensitive line rat model of depression—25 years and still producing. Pharmacol Rev 65:143–155

    Article  PubMed  CAS  Google Scholar 

  • Overstreet DH, Friedman E, Mathe AA, Yadid G (2005) The Flinders sensitive line rat: a selectively bred putative animal model of depression. Neurosci Biobehav Rev 29:739–759

    Article  PubMed  CAS  Google Scholar 

  • Palanza P (2001) Animal models of anxiety and depression: how are females different? Neurosci Biobehav Rev 25:219–233

    Article  PubMed  CAS  Google Scholar 

  • Pariante CM, Lightman SL (2008) The HPA axis in major depression: classical theories and new developments. Trends Neurosci 31:464–468

    Article  PubMed  CAS  Google Scholar 

  • Plotsky PM, Meaney MJ (1993) Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Brain Res Mol Brain Res 18:195–200

    Article  PubMed  CAS  Google Scholar 

  • Pollak DD, Rey CE, Monje FJ (2010) Rodent models in depression research: classical strategies and new directions. Ann Med 42:252–264

    Article  PubMed  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977a) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    PubMed  CAS  Google Scholar 

  • Porsolt RD, Le Pichon M, Jalfre M (1977b) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732

    Article  PubMed  CAS  Google Scholar 

  • Pryce CR, Feldon J (2003) Long-term neurobehavioural impact of the postnatal environment in rats: manipulations, effects and mediating mechanisms. Neurosci Biobehav Rev 27:57–71

    Article  PubMed  Google Scholar 

  • Pryce CR, Seifritz E (2011) A translational research framework for enhanced validity of mouse models of psychopathological states in depression. Psychoneuroendocrinology 36:308–329

    Article  PubMed  Google Scholar 

  • Pryce CR, Azzinnari D, Spinelli S, Seifritz E, Tegethoff M, Meinlschmidt G (2011) Helplessness: a systematic translational review of theory and evidence for its relevance to understanding and treating depression. Pharmacol Ther 132:242–267

    Article  PubMed  CAS  Google Scholar 

  • Pryce CR, Azzinnari D, Sigrist H, Gschwind T, Lesch KP, Seifritz E (2012) Establishing a learned-helplessness effect paradigm in C57BL/6 mice: behavioural evidence for emotional, motivational and cognitive effects of aversive uncontrollability per se. Neuropharmacology 62:358–372

    Article  PubMed  CAS  Google Scholar 

  • Raison CL, Miller AH (2011) Is depression an inflammatory disorder? Curr Psychiatry Rep 13:467–475

    Article  PubMed  Google Scholar 

  • Rajkowska G (2000) Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 48:766–777

    Article  PubMed  CAS  Google Scholar 

  • Reichardt HM, Kaestner KH, Wessely O, Gass P, Schmid W, Schutz G (1998) Analysis of glucocorticoid signalling by gene targeting. J Steroid Biochem Mol Biol 65:111–115

    Article  PubMed  CAS  Google Scholar 

  • Ressler KJ, Nemeroff CB (2000) Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety 12 (Suppl 1):2–19

    Article  PubMed  Google Scholar 

  • Richardson-Jones JW, Craige CP, Guiard BP, Stephen A, Metzger KL, Kung HF, Gardier AM, Dranovsky A, David DJ, Beck SG, Hen R, Leonardo ED (2010) 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron 65:40–52

    Article  PubMed  CAS  Google Scholar 

  • Richter SH, Schick A, Hoyer C, Lankisch K, Gass P, Vollmayr B (2012) A glass full of optimism: enrichment effects on cognitive bias in a rat model of depression. Cogn Affect Behav Neurosci 12:527–542

    Article  PubMed  Google Scholar 

  • Roose SP, Glassman AH, Attia E, Woodring S (1994) Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Am J Psychiatry 151:1735–1739

    PubMed  CAS  Google Scholar 

  • Samuels BA, Leonardo ED, Gadient R, Williams A, Zhou J, David DJ, Gardier AM, Wong EH, Hen R (2011) Modeling treatment-resistant depression. Neuropharmacology 61:408–413

    Article  PubMed  CAS  Google Scholar 

  • Savignac HM, Finger BC, Pizzo RC, O’Leary OF, Dinan TG, Cryan JF (2011) Increased sensitivity to the effects of chronic social defeat stress in an innately anxious mouse strain. Neuroscience 192:524–536

    Article  PubMed  CAS  Google Scholar 

  • Seligman ME, Beagley G (1975) Learned helplessness in the rat. J Comp Physiol Psychol 88:534–541

    Article  PubMed  CAS  Google Scholar 

  • Sheline YI, Mittler BL, Mintun MA (2002) The hippocampus and depression. Eur Psychiatry 17 (Suppl 3):300–305

    Article  PubMed  Google Scholar 

  • Sherman AD, Sacquitne JL, Petty F (1982) Specificity of the learned helplessness model of depression. Pharmacol Biochem Behav 16:449–454

    Article  PubMed  CAS  Google Scholar 

  • Slattery DA, Markou A, Cryan JF (2007) Evaluation of reward processes in an animal model of depression. Psychopharmacology (Berl) 190:555–568

    Article  CAS  Google Scholar 

  • Slattery DA, Neumann ID, Cryan JF (2011) Transient inactivation of the infralimbic cortex induces antidepressant-like effects in the rat. J Psychopharmacol 25:1295–1303

    Article  PubMed  Google Scholar 

  • Slattery DA, Uschold N, Magoni M, Bar J, Popoli M, Neumann ID, Reber SO (2012) Behavioural consequences of two chronic psychosocial stress paradigms: anxiety without depression. Psychoneuroendocrinology 37:702–714

    Article  PubMed  Google Scholar 

  • Smith DJ, Kyle S, Forty L, Cooper C, Walters J, Russell E, Caesar S, Farmer A, McGuffin P, Jones I, Jones L, Craddock N (2008) Differences in depressive symptom profile between males and females. J Affect Disord 108:279–284

    Article  PubMed  Google Scholar 

  • Song C, Leonard BE (2005) The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev 29:627–647

    Article  PubMed  Google Scholar 

  • Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) 85:367–370

    Article  CAS  Google Scholar 

  • Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, Vaugeois JM, Nomikos GG, Greengard P (2006) Alterations in 5-HT1B receptor function by p11 in depression-like states. Science 311:77–80

    Article  PubMed  CAS  Google Scholar 

  • Tejani-Butt SM, Pare WP, Yang J (1994) Effect of repeated novel stressors on depressive behavior and brain norepinephrine receptor system in Sprague–Dawley and Wistar Kyoto (WKY) rats. Brain Res 649:27–35

    Article  PubMed  CAS  Google Scholar 

  • Ter Horst GJ, Wichmann R, Gerrits M, Westenbroek C, Lin Y (2009) Sex differences in stress responses: focus on ovarian hormones. Physiol Behav 97:239–249

    Article  PubMed  CAS  Google Scholar 

  • Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M (2006) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 163:28–40

    Article  PubMed  Google Scholar 

  • Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525

    Article  PubMed  CAS  Google Scholar 

  • Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai HC, Finkelstein J, Kim SY, Adhikari A, Thompson KR, Andalman AS, Gunaydin LA, Witten IB, Deisseroth K (2013) Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493:537–541

    Article  PubMed  CAS  Google Scholar 

  • Uher R (2008) The implications of gene-environment interactions in depression: will cause inform cure? Mol Psychiatry 13:1070–1078

    Article  PubMed  CAS  Google Scholar 

  • Uher R, Caspi A, Houts R, Sugden K, Williams B, Poulton R, Moffitt TE (2011) Serotonin transporter gene moderates childhood maltreatment’s effects on persistent but not single-episode depression: replications and implications for resolving inconsistent results. J Affect Disord 135:56–65

    Article  PubMed  CAS  Google Scholar 

  • Urani A, Chourbaji S, Gass P (2005) Mutant mouse models of depression: candidate genes and current mouse lines. Neurosci Biobehav Rev 29:805–828

    Article  PubMed  CAS  Google Scholar 

  • Van den Hove DL, Kenis G, Brass A, Opstelten R, Rutten BP, Bruschettini M, Blanco CE, Lesch KP, Steinbusch HW, Prickaerts J (2012) Vulnerability versus resilience to prenatal stress in male and female rats; implications from gene expression profiles in the hippocampus and frontal cortex. Eur Neuropsychopharmacol (in press)

  • Vogel G, Neill D, Kors D, Hagler M (1990) REM sleep abnormalities in a new animal model of endogenous depression. Neurosci Biobehav Rev 14:77–83

    Article  PubMed  CAS  Google Scholar 

  • Vollmayr B, Bachteler D, Vengeliene V, Gass P, Spanagel R, Henn F (2004) Rats with congenital learned helplessness respond less to sucrose but show no deficits in activity or learning. Behav Brain Res 150:217–221

    Article  PubMed  CAS  Google Scholar 

  • Warden MR, Selimbeyoglu A, Mirzabekov JJ, Lo M, Thompson KR, Kim SY, Adhikari A, Tye KM, Frank LM, Deisseroth K (2012) A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge. Nature 492:428–432

    PubMed  CAS  Google Scholar 

  • WHO (2004) The global burden of disease: 2004 update. World Health Organisation, Geneva

    Google Scholar 

  • Willner P (1997) Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 134:319–329

    Article  CAS  Google Scholar 

  • Yu H, Wang DD, Wang Y, Liu T, Lee FS, Chen ZY (2012) Variant brain-derived neurotrophic factor Val66Met polymorphism alters vulnerability to stress and response to antidepressants. J Neurosci 32:4092–4101

    Article  PubMed  CAS  Google Scholar 

  • Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856–864

    Article  PubMed  CAS  Google Scholar 

  • Zarate CA Jr, Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I, Jolkovsky L, Brutsche NE, Smith MA, Luckenbaugh DA (2012) A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression. Biol Psychiatry. doi:10.1016/j.biopsych.2012.10.019

  • Zarate CA, Mathews DC, Furey ML (2013) Human biomarkers of rapid antidepressant effects. Biol Psychiatry. doi:10.1016/j.biopsych.2012.11.031

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland

    Olivia F. O’Leary & John F. Cryan

  2. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

    John F. Cryan

Authors
  1. Olivia F. O’Leary
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John F. Cryan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Olivia F. O’Leary or John F. Cryan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Leary, O.F., Cryan, J.F. Towards translational rodent models of depression. Cell Tissue Res 354, 141–153 (2013). https://doi.org/10.1007/s00441-013-1587-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-013-1587-9

Keywords

Search

Navigation