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Modeling Human Anxiety and Depression in Mutant Mice

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Transgenic and Knockout Models of Neuropsychiatric Disorders

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

Mood and anxiety disorders represent some of the most common and proliferating health problems worldwide, but are inadequately treated by existing therapeutic interventions. Valid animal models of anxiety and depression have a critical role to play in identifying novel therapeutic targets for these debilitating conditions. The emergence of techniques that allow genetic manipulation of specific molecules in mice has added a valuable new dimension to this field of research. In this chapter, we discuss some of the conceptual issues surrounding the use of mutant mice to study anxiety and depression, the behavioral tasks commonly used for assessment, and important caveats associated with the use of mutant mice. Anxietyrelated behavior is most commonly assayed in mice using tests based on exploratory approach/ avoid conflict (e.g., elevated plus maze, open field, light-dark exploration, and hyponeophagia), although a variety of alternatives exist (e.g., stress-induced hyperthermia, mouse defense test battery, Vogel conflict, shock-probe burying, four-plate test, marble burying, and separation-induced pup ultrasonic vocalizations). Mouse tests for depressionrelated behaviors include models based on “behavioral despair” (forced-swim test, tail-suspension test, and learned helplessness), as well as chronic mild stress, olfactory bulbectomy, and psychostimulant withdrawal. Various factors can confound performance and complicate interpretation of the behavior of mutant mice on anxiety- and depression-related tasks, including genetic background, abnormal motor and sensory phenotypes, previous test history, and variability in early life environment and parental behavior. In addition, lifelong constitutive mutations can recruit compensatory changes that occlude the normal function of a molecule in neural circuits mediating emotion-related behaviors. Mutant mice provide a particularly valuable approach to the study of anxiety disorders and depression and their treatment when used in conjunction with other techniques to generate converging lines of evidence regarding the role of a molecule in these circuits. When viewed as such, we believe that mutant mice will continue to foster the study of anxiety and depression.

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References

  1. Andrade L, Caraveo-Anduaga JJ, Berglund P, et al. The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int J Methods Psychiatr Res 2003;12:3–21.

    PubMed  Google Scholar 

  2. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289:3095–3105.

    PubMed  Google Scholar 

  3. Association AP. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. Washington, DC: American Psychiatric Association, 2000.

    Google Scholar 

  4. Levi F, La Vecchia C, Saraceno B. Global suicide rates. Eur J Public Health 2003;13:97–98.

    PubMed  Google Scholar 

  5. Williams LS, Ghose SS, Swindle RW. Depression and other mental health diagnoses increase mortality risk after ischemic stroke. Am J Psychiatry 2004;161:1090–1095.

    PubMed  Google Scholar 

  6. Greenberg PE, Kessler RC, Birnbaum HG, et al. The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry 2003;64:1465–1475.

    PubMed  Google Scholar 

  7. Holmes A, Heilig M, Rupniak NM, Steckler T, Griebel G. Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol Sci 2003;24:580–588.

    PubMed  CAS  Google Scholar 

  8. Insel TR, Charney DS. Research on major depression: strategies and priorities. JAMA 2003;289:3167–3168.

    PubMed  Google Scholar 

  9. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1970;23:51–56.

    Google Scholar 

  10. Geyer MA, Markou A. The Role of Preclinical Models in the Development of Psychotropic Drugs. In: Kupfer DJ, ed. Psychopharmacology: The Fifth Generation of Progress. New York: Raven, 2000.

    Google Scholar 

  11. McKinney WT. Overview of the past contributions of animal models and their changing place in psychiatry. Semin Clin Neuropsychiatry 2001;6:68–78.

    PubMed  CAS  Google Scholar 

  12. Rodgers RJ. Animal models of ‘anxiety’: where next? Behav Pharmacol 1997;8:477–96;discussion 497-504.

    PubMed  CAS  Google Scholar 

  13. Willner P. Animal models of depression: an overview. Pharmacol Ther 1990;45:425–455.

    PubMed  CAS  Google Scholar 

  14. McKinney WTJr, Bunney WEJr. Animal model of depression. I. Review of evidence: implications for research. Arch Gen Psychiatry 1969;21:240–248.

    PubMed  Google Scholar 

  15. Bucan M. Abel T. The mouse: genetics meets behaviour. Nat Rev Genet 2002;3:114–123.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  17. Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 2002;23:238–245.

    PubMed  CAS  Google Scholar 

  18. Holmes A. Targeted gene mutation approaches to the study of anxiety-like behavior in mice. Neurosci Biobehav Rev 2001;25;261–273.

    PubMed  CAS  Google Scholar 

  19. Lesch KP, Zeng Y, Reif A, Gutknecht L. Anxiety-related traits in mice with modified genes of the serotonergic pathway. Eur J Pharmacol 2003;480:185–204.

    PubMed  CAS  Google Scholar 

  20. Finn DA, Rutledge-Gorman MT, Crabbe JC. Genetic animal models of anxiety. Neurogenetics 2003;4:109–135.

    PubMed  Google Scholar 

  21. Nesse RM. Is depression an adaptation? Arch Gen Psychiatry 2000;57:14–20.

    PubMed  CAS  Google Scholar 

  22. File SE, Seth P. A review of 25 years of the social interaction test. Eur J Pharmacol 2003;463:35–53.

    PubMed  CAS  Google Scholar 

  23. Risbrough VB, Brodkin JD, Geyer MA. GABA-A and 5-HT1A receptor agonists block expression of fear-potentiated startle in mice. Neuropsychopharmacology 2003;28:654–663.

    PubMed  CAS  Google Scholar 

  24. Crawley JN. Neuropharmacologic specificity of a simple animal model for the behavioral actions of benzodiazepines. Pharmacol Biochem Behav 1981;15:695–699.

    PubMed  CAS  Google Scholar 

  25. Zethof TJ, Van der Heyden JA, Tolboom JT, Olivier B. Stress-induced hyperthermia in mice: a methodological study. Physiol Behav 1994;55:109–115.

    PubMed  CAS  Google Scholar 

  26. Rodgers RJ, Cao BJ, Dalvi A, Holmes A. Animal models of anxiety: an ethological perspective. Braz J Med Biol Res 1997;30:289–304.

    PubMed  CAS  Google Scholar 

  27. Belzung C, Griebel G. Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 2001;125:141–149.

    PubMed  CAS  Google Scholar 

  28. Falzone TL, Gelman DM, Young JI, Grandy DK, Low MJ, Rubinstein M. Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear. Eur J Neurosci 2002;15:158–164.

    PubMed  Google Scholar 

  29. Dulawa SC, Grandy DK, Low MJ, Paulus MP, Geyer MA. Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. J Neurosci 1999;19:9550–9556.

    PubMed  CAS  Google Scholar 

  30. Blanchard DC, Griebel G, Blanchard RJ. The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic. Eur J Pharmacol 2003;463:97–116.

    PubMed  CAS  Google Scholar 

  31. van Gaalen MM, Stenzel-Poore MP, Holsboer F, Steckler T. Effects of transgenic overproduction of CRH on anxiety-like behaviour. Eur J Neurosci 2002;15:2007–2015.

    PubMed  Google Scholar 

  32. Santarelli L, Gobbi G, Debs PC, et al. Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function. Proc Natl Acad Sci USA 2001;98:1912–1917.

    PubMed  CAS  Google Scholar 

  33. Degroot A, Nomikos GG. Genetic deletion and pharmacological blockade of CB1 receptors modulates anxiety in the shock-probe burying test. Eur J Neurosci 2004;20:1059–1064.

    PubMed  Google Scholar 

  34. Hascoet M, Bourin M, Couetoux du Tertre A. Influence of prior experience on mice behavior using the four-plate test. Pharmacol Biochem Behav 1997;58:1131–1138.

    PubMed  CAS  Google Scholar 

  35. Chaki S, Hirota S, Funakoshi T, et al. Anxiolytic-like and antidepressant-like activities of MCL0129 (1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-met hoxynaphthalen-1-yl)butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor. J Pharmacol Exp Ther 2003;304:818–826.

    PubMed  CAS  Google Scholar 

  36. Dirks A, Fish EW, Kikusui T, et al. Effects of corticotropin-releasing hormone on distress vocalizations and locomotion in maternally separated mouse pups. Pharmacol Biochem Behav 2002;72:993–999.

    PubMed  CAS  Google Scholar 

  37. Crawley JN. Whats wrong with my mouse? Behavioral Phenotyping of Transgenic and Knockout Mice. New York: Wiley-Liss, 2000.

    Google Scholar 

  38. Holmes A, Yang RJ, Murphy DL, Crawley JN. Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology 2002;27:914–923.

    PubMed  CAS  Google Scholar 

  39. Salas R, Pieri F, Fung B, Dani JA, De Biasi M. Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor. J Neurosci 2003;23:6255–6263.

    PubMed  CAS  Google Scholar 

  40. Holmes A, Kinney JW, Wrenn CC, et al. Galanin GAL-R1 receptor null mutant mice display increased anxiety-like behavior specific to the elevated plus-maze. Neuropsychopharmacology 2003;28:1031–1044.

    PubMed  CAS  Google Scholar 

  41. van Gaalen MM, Steckler T. Behavioural analysis of four mouse strains in an anxiety test battery. Behav Brain Res 2000;115:95–106.

    PubMed  Google Scholar 

  42. Bale TL, Contarino A, Smith GW, et al. Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet 2000;24:410–414.

    PubMed  CAS  Google Scholar 

  43. Coste SC, Kesterson RA, Heldwein KA, et al. Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Nat Genet 2000;24:403–409.

    PubMed  CAS  Google Scholar 

  44. Kishimoto T, Radulovic J, Radulovic M, et al. Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2. Nat Genet 2000;24:415–419.

    PubMed  CAS  Google Scholar 

  45. Turri MG, Datta SR, DeFries J, Henderson ND, Flint J. QTL analysis identifies multiple behavioral dimensions in ethological tests of anxiety in laboratory mice. Curr Biol 2001;11:725–734.

    PubMed  CAS  Google Scholar 

  46. Lang PJ, Davis M, Ohman A. Fear and anxiety: animal models and human cognitive psycho-physiology. J Affect Disord 2000;61:137–159.

    PubMed  CAS  Google Scholar 

  47. Kim JJ, Fanselow MS. Modality-specific retrograde amnesia of fear. Science 1992;256:675–677.

    PubMed  CAS  Google Scholar 

  48. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci 2000;23:155–184.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  50. Eysenck MW. Anxiety and Cognition: A Unified Theory. Hove, England: Psychology Press, 1997.

    Google Scholar 

  51. Crestani F, Lorez M, Baer K, et al. Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues. Nat Neurosci 1999;2:833–839.

    PubMed  CAS  Google Scholar 

  52. Cain CK, Blouin AM, Barad M. L-type voltage-gated calcium channels are required for extinction, but not for acquisition or expression, of conditional fear in mice. J Neurosci 2002;22:9113–9121.

    PubMed  CAS  Google Scholar 

  53. El-Ghundi M, O’Dowd BF, George SR. Prolonged fear responses in mice lacking dopamine D1 receptor. Brain Res 2001;892:86–93.

    PubMed  CAS  Google Scholar 

  54. Anisman H, Zacharko RM. Multiple neurochemical and behavioral consequences of stressors: implications for depression. Pharmacol Ther 1990;46:119–136.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  56. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 2000;157:1552–1562.

    PubMed  CAS  Google Scholar 

  57. Wong ML, Licinio J. Research and treatment approaches to depression. Nat Rev Neurosci 2001;2:343–351.

    PubMed  CAS  Google Scholar 

  58. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002;34:13–25.

    PubMed  CAS  Google Scholar 

  59. Geyer MA, Markou A. Animal Models of Psychiatric Disorders. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York, Raven Press, 1995, pp. 787–798.

    Google Scholar 

  60. Geyer MA, Markou A. The Role of Preclinical Models in the Development of Psychotropic Drugs. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fifth Generation of Progress. New York, Raven, 2000.

    Google Scholar 

  61. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;160:636–645.

    PubMed  Google Scholar 

  62. Hyman SE, Fenton WS. Medicine. What are the right targets for psychopharmacology? Science 2003;299:350–351.

    PubMed  CAS  Google Scholar 

  63. Inoue K, Lupski JR. Genetics and genomics of behavioral and psychiatric disorders. Curr Opin Genet Dev 2003;13:303–309.

    PubMed  CAS  Google Scholar 

  64. Hassler G, Drevets W, Manji H, Charney D. Discovering endophenotypes for major depression. Neuropsychopharmacology, 2004, in press.

    Google Scholar 

  65. Porsolt RD. Animal models of depression: utility for transgenic research. Rev Neurosci 2000;11:53–58.

    PubMed  CAS  Google Scholar 

  66. Seong E, Seasholtz AF, Burmeister M. Mouse models for psychiatric disorders. Trends Genet 2002;18:643–650.

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  68. Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepres-sant activity: Review of pharmacological and genetic studies in mice. Neuroscience and Biobehavioral Reviews, 2004, in press.

    Google Scholar 

  69. Bai F, Li X, Clay M, Lindstrom T, Skolnick P. Intra-and interstrain differences in models of “behavioral despair”. Pharmacol Biochem Behav 2001;70:187–192.

    PubMed  CAS  Google Scholar 

  70. Renard CE, Dailly E, David DJ, Hascoet M, Bourin M. Monoamine metabolism changes following the mouse forced swimming test but not the tail suspension test. Fundam Clin Pharmacol 2003;17:449–455.

    PubMed  CAS  Google Scholar 

  71. Liu X, Peprah D, Gershenfeld HK. Tail-suspension induced hyperthermia: a new measure of stress reactivity. J Psychiatr Res 2003;37:249–259.

    PubMed  Google Scholar 

  72. Lucki I, Dalvi A, Mayorga AJ. Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology (Berl) 2001;155:315–322.

    CAS  Google Scholar 

  73. Porsolt R, Lenegre A. Behavioral Models of Ddepression. In: Elliott J, Heal D, Marsden C, eds. Experimental Approaches to Anxiety and Depression. London, Wiley, 1992, pp. 73–85.

    Google Scholar 

  74. Mombereau C, Kaupmann K, Froestl W, Sansig G, Van Der Putten H, Cryan JF. Genetic and Pharmacological evidence of a role for GABA(B) receptors in the modulation of anxiety-and antidepressant-like behavior. Neuropsychopharmacology 2004;29:1050–1062.

    PubMed  CAS  Google Scholar 

  75. Thierry B, Steru L, Chermat R, Simon P. Searching-waiting strategy: a candidate for an evolutionary model of depression? Behav Neural Biol 1984;41:180–189.

    PubMed  CAS  Google Scholar 

  76. Dixon AK. Ethological strategies for defence in animals and humans: their role in some psychiatric disorders. Br J Med Psychol 1998;71(Pt 4):417–445.

    PubMed  Google Scholar 

  77. Gilbert P, Allan S. The role of defeat and entrapment (arrested flight) in depression: an exploration of an evolutionary view. Psychol Med 1998;28:585–598.

    PubMed  CAS  Google Scholar 

  78. Lucki I. A prescription to resist proscriptions for murine models of depression. Psychopharmacology (Berl) 2001;153:395–398.

    CAS  Google Scholar 

  79. Weingartner H, Silberman E. Models of cognitive impairment: cognitive changes in depression. Psychopharmacol Bull 1982;18:27–42.

    PubMed  CAS  Google Scholar 

  80. Nishimura H, Tsuda A, Oguchi M, Ida Y, Tanaka M. Is immobility of rats in the forced swim test “behavioral despair”? Physiol Behav 1988;42:93–95.

    PubMed  CAS  Google Scholar 

  81. West CH, Weiss JM. Effects of antidepressant drugs on rats bred for low activity in the swim test. Pharmacol Biochem Behav 1998;61:67–79.

    PubMed  CAS  Google Scholar 

  82. Solberg LC, Horton TH, Turek FW. Circadian rhythms and depression: effects of exercise in an animal model. Am J Physiol 1999;276:R152–R161.

    PubMed  CAS  Google Scholar 

  83. Alonso SJ, Damas C, Navarro E. Behavioral despair in mice after prenatal stress. J Physiol Biochem 2000;56:77–82.

    PubMed  CAS  Google Scholar 

  84. Tannenbaum B, Tannenbaum GS, Sudom K, Anisman H. Neurochemical and behavioral alterations elicited by a chronic intermittent stressor regimen: implications for allostatic load. Brain Res 2002;953:82–92.

    PubMed  CAS  Google Scholar 

  85. Alcaro A, Cabib S, Ventura R, Puglisi-Allegra S. Genotype-and experience-dependent susceptibility to depressive-like responses in the forced-swimming test. Psychopharmacology (Berl) 2002;164:138–143.

    CAS  Google Scholar 

  86. Kokkinidis L, Zacharko RM, Anisman H. Amphetamine withdrawal: a behavioral evaluation. Life Sci 1986;38:1617–1623.

    PubMed  CAS  Google Scholar 

  87. Cryan JF, Hoyer D, Markou A. Withdrawal from chronic amphetamine induces Depressive-Like behavioral effects in rodents. Biol Psychiatry 2003;54:49–58.

    PubMed  CAS  Google Scholar 

  88. Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. EurJ Pharmacol 1978;47:379–391.

    CAS  Google Scholar 

  89. Borsini F, Meli A. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology (Berl) 1988;94:147–160.

    CAS  Google Scholar 

  90. Miyakawa T, Yamada M, Duttaroy A, Wess J. Hyperactivity and intact hippocampus-dependent learning in mice lacking the M1 muscarinic acetylcholine receptor. J Neurosci 2001;21:5239–5250.

    PubMed  CAS  Google Scholar 

  91. Overmier JB, Seligman ME. Effects of inescapable shock upon subsequent escape and avoidance responding. J Comp Physiol Psychol 1967;63:28–33.

    PubMed  CAS  Google Scholar 

  92. Seligman ME, Maier SF. Failure to escape traumatic shock. J Exp Psychol 1967;74:1–9.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  94. Anisman H, Irwin J, Sklar LS. Deficits of escape performance following catecholamine depletion: implications for behavioral deficits induced by uncontrollable stress. Psychopharmacology (Berl) 1979;64:163–170.

    CAS  Google Scholar 

  95. Anisman H, DeCatanzaro D, Remington G. Escape performance following exposure to inescapable shock: Deficits in motor response maintenance. J Exp Psychol Anim Behav Process 1978;4:197–218.

    Google Scholar 

  96. Leshner AI, Remler H, Biegon A, Samuel D. Desmethylimipramine (DMI) counteracts learned helplessness in rats. Psychopharmacology (Berl) 1979;66:207–208.

    CAS  Google Scholar 

  97. Sherman AD, Petty F. Additivity of neurochemical changes in learned helplessness and imi-pramine. Behav Neural Biol 1982;35:344–353.

    PubMed  CAS  Google Scholar 

  98. Martin P, Soubrie P, Puech AJ. Reversal of helpless behavior by serotonin uptake blockers in rats. Psychopharmacology (Berl) 1990;101:403–407.

    CAS  Google Scholar 

  99. Weiss JM, Kilts CD. Animal Models of Depression and Schizophrenia. In: Nemeroff CB, Schatzberg AF, eds. Textbook of Psychopharmacology. 2nd ed. American Psychiatric Press, 1998, pp. 88–123.

    Google Scholar 

  100. Caldarone BJ, George TP, Zachariou V, Picciotto MR. Gender differences in learned helplessness behavior are influenced by genetic background. Pharmacol Biochem Behav 2000;66:811–817.

    PubMed  CAS  Google Scholar 

  101. Drugan RC, Skolnick P, Paul SM, Crawley JN. A pretest procedure reliably predicts performance in two animal models of inescapable stress. Pharmacol Biochem Behav 1989;33:649–654.

    PubMed  CAS  Google Scholar 

  102. Vollmayr B, Henn FA. Learned helplessness in the rat: improvements in validity and reliability. Brain Res Brain Res Protoc 2001;8:1–7.

    PubMed  CAS  Google Scholar 

  103. Shanks N, Anisman H. Escape deficits induced by uncontrollable foot-shock in recombinant inbred strains of mice. Pharmacol Biochem Behav 1993;46:511–517.

    PubMed  CAS  Google Scholar 

  104. Shanks N, Anisman H. Strain-specific effects of antidepressants on escape deficits induced by inescapable shock. Psychopharmacology (Berl) 1989;99:122–128.

    CAS  Google Scholar 

  105. Shanks N, Anisman H. Stressor-provoked behavioral changes in six strains of mice. Behav Neurosci 1988;102:894–905.

    PubMed  CAS  Google Scholar 

  106. Mogil JS, Wilson SG, Bon K, et al. Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception. Pain 1999;80:67–82.

    PubMed  CAS  Google Scholar 

  107. MacQueen GM, Ramakrishnan K, Croll SD, et al. Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression. Behav Neurosci 2001;115:1145–1153.

    PubMed  CAS  Google Scholar 

  108. Willner P, Muscat R, Papp M. An animal model of anhedonia. Clin Neuropharmacol 1992;15(Suppl 1, Pt A):550A–551A.

    PubMed  Google Scholar 

  109. Willner P, Muscat R, Papp M. Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 1992;16:525–534.

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  111. Moreau JL, Jenck F, Martin JR, Mortas P, Haefely WE. Antidepressant treatment prevents chronic unpredictable mild stress-induced anhedonia as assessed by ventral tegmentum self-stimulation behavior in rats. Eur Neuropsychopharmacol 1992;2:43–49.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  114. Reid I, Forbes N, Stewart C, Matthews K. Chronic mild stress and depressive disorder: a useful new model? Psychopharmacology (Berl) 1997;134:365–367;discussion 371-377.

    CAS  Google Scholar 

  115. Hatcher JP, Bell DJ, Reed TJ, Hagan JJ. Chronic mild stress-induced reductions in saccharin intake depend upon feeding status. J Psychopharmacol 1997;11:331–338.

    PubMed  CAS  Google Scholar 

  116. Harris RB, Zhou J, Youngblood BD, Smagin GN, Ryan DH. Failure to change exploration or saccharin preference in rats exposed to chronic mild stress. Physiol Behav 1997;63:91–100.

    PubMed  CAS  Google Scholar 

  117. Nielsen CK, 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.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  120. Barr AM, Zis AP, Phillips AG. Repeated electroconvulsive shock attenuates the depressive-like effects of d-amphetamine withdrawal on brain reward function in rats. Psychopharmacology (Berl) 2002;159:196–202.

    CAS  Google Scholar 

  121. Bielajew C, Konkle AT, Merali Z. The effects of chronic mild stress on male Sprague-Dawley and Long Evans rats:I. Biochemical and physiological analyses. Behav Brain Res 2002;136:583–592.

    PubMed  CAS  Google Scholar 

  122. Harkin A, Houlihan DD, Kelly JP. Reduction in preference for saccharin by repeated unpredictable stress in mice and its prevention by imipramine. J Psychopharmacol 2002;16:115–123.

    PubMed  CAS  Google Scholar 

  123. Ducottet C, Griebel G, Belzung C. 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 2003;27:625–631.

    PubMed  CAS  Google Scholar 

  124. Griebel G, Simiand J, Serradeil-Le Gal C, et al. Anxiolytic-and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci USA 2002;99:6370–6375.

    PubMed  CAS  Google Scholar 

  125. Griebel G, Simiand J, Steinberg R, et al. 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1, 3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factor(1) receptor antagonist. II. Characterization in rodent models of stress-related disorders. J Pharmacol Exp Ther 2002;301:333–345.

    PubMed  CAS  Google Scholar 

  126. Jesberger JA, Richardson JS. Brain output dysregulation induced by olfactory bulbectomy: an approximation in the rat of major depressive disorder in humans? Int J Neurosci 1988;38:241–265.

    PubMed  CAS  Google Scholar 

  127. Kelly JP, Wrynn AS, Leonard BE. The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 1997;74:299–316.

    PubMed  CAS  Google Scholar 

  128. Lumia AR, Teicher MH, Salchli F, Ayers E, Possidente B. Olfactory bulbectomy as a model for agitated hyposerotonergic depression. Brain Res 1992;587:181–185.

    PubMed  CAS  Google Scholar 

  129. van Riezen H, Leonard BE. Effects of psychotropic drugs on the behavior and neurochemistry of olfactory bulbectomized rats. Pharmacol Ther 1990;47:21–34.

    PubMed  Google Scholar 

  130. Neckers LM, Zarrow MX, Myers MM, Denenberg VH. Influence of olfactory bulbectomy and the serotonergic system upon intermale aggression and maternal behavior in the mouse. Pharmacol Biochem Behav 1975;3:545–550.

    PubMed  CAS  Google Scholar 

  131. Otmakhova NA, Gurevich EV, Katkov YA, Nesterova IV, Bobkova NV. Dissociation of multiple behavioral effects between olfactory bulbectomized C57Bl/6J and DBA/2J mice. Physiol Behav 1992;52:441–448.

    PubMed  CAS  Google Scholar 

  132. Gurevich EV, Aleksandrova IA, Otmakhova NA, Katkov YA, Nesterova IV, Bobkova NV. Effects of bulbectomy and subsequent antidepressant treatment on brain 5-HT2 and 5-HT1A receptors in mice. Pharmacol Biochem Behav 1993;45:65–70.

    PubMed  CAS  Google Scholar 

  133. Possidente B, Lumia AR, McGinnis MY, Rapp M, McEldowney S. Effects of fluoxetine and olfactory bulbectomy on mouse circadian activity rhythms. Brain Res 1996;713:108–113.

    PubMed  CAS  Google Scholar 

  134. Nesterova IV, Gurevich EV, Nesterov VI, Otmakhova NA, Bobkova NV. Bulbectomy-induced loss of raphe neurons is counteracted by antidepressant treatment. Prog Neuropsychopharmacol Biol Psychiatry 1997;21:127–140.

    PubMed  CAS  Google Scholar 

  135. Komori T, Yamamoto M, Matsumoto T, Zhang K, Okazaki Y. Effects of imipramine on T cell subsets in olfactory bulbectomized mice. Neuropsychobiology 2002;46:194–196.

    PubMed  CAS  Google Scholar 

  136. Bilkei-Gorzo A, Racz I, Michel K, Zimmer A. Diminished anxiety-and depression-related behaviors in mice with selective deletion of the Tac1 gene. J Neurosci 2002;22:10,046–10,052.

    PubMed  CAS  Google Scholar 

  137. Hozumi S, Nakagawasai O, Tan-No K, et al. Characteristics of changes in cholinergic function and impairment of learning and memory-related behavior induced by olfactory bulbectomy. Behav Brain Res 2003;138:9–15.

    PubMed  CAS  Google Scholar 

  138. Cryan JF, McGrath C, Leonard BE, Norman TR. Combining pindolol and paroxetine in an animal model of chronic antidepressant action:-can early onset of action be detected? Eur J Pharmacol 1998;352:23–28.

    PubMed  CAS  Google Scholar 

  139. Cryan JF, McGrath C, Leonard BE, Norman TR. Onset of the effects of the 5-HT1A antagonist, WAY-100635, alone, and in combination with paroxetine, on olfactory bulbectomy and 8-OH-DPAT-induced changes in the rat. Pharmacol Biochem Behav 1999;63:333–338.

    PubMed  CAS  Google Scholar 

  140. Stock HS, Hand GA, Ford K, Wilson MA. Changes in defensive behaviors following olfactory bulbectomy in male and female rats. Brain Res 2001;903:242–246.

    PubMed  CAS  Google Scholar 

  141. Primeaux SD, Holmes PV. Role of aversively motivated behavior in the olfactory bulbectomy syndrome. Physiol Behav 1999;67:41–47.

    PubMed  CAS  Google Scholar 

  142. Mar A, Spreekmeester E, Rochford J. Antidepressants preferentially enhance habituation to novelty in the olfactory bulbectomized rat. Psychopharmacology (Berl) 2000;150:52–60.

    CAS  Google Scholar 

  143. McNish KA, Davis M. Olfactory bulbectomy enhances sensitization of the acoustic startle reflex produced by acute or repeated stress. Behav Neurosci 1997;111:80–91.

    PubMed  CAS  Google Scholar 

  144. van Rijzingen IM, Gispen WH, Spruijt BM. Olfactory bulbectomy temporarily impairs Morris maze performance: an ACTH(4-9) analog accelerates return of function. Physiol Behav 1995;58:147–52.

    PubMed  Google Scholar 

  145. Marcilhac A, Anglade G, Hery F, Siaud P. Olfactory bulbectomy increases vasopressin, but not corticotropin-releasing hormone, content in the external layer of the median eminence of male rats. Neurosci Lett 1999;262:89–92.

    PubMed  CAS  Google Scholar 

  146. Marcilhac A, Faudon M, Anglade G, Hery F, Siaud P. An investigation of serotonergic involvement in the regulation of ACTH and corticosterone in the olfactory bulbectomized rat. Pharmacol Biochem Behav 1999;63:599–605.

    PubMed  CAS  Google Scholar 

  147. Stock HS, Ford K, Wilson MA. Gender and gonadal hormone effects in the olfactory bulbectomy animal model of depression. Pharmacol Biochem Behav 2000;67:183–191.

    PubMed  CAS  Google Scholar 

  148. Holmes PV, Masini CV, Primeaux SD, et al. Intravenous self-administration of amphetamine is increased in a rat model of depression. Synapse 2002;46:4–10.

    PubMed  CAS  Google Scholar 

  149. Katkov YA, Otmakhova NA, Gurevich EV, Nesterova IV, Bobkova NV. Antidepressants suppress bulbectomy-induced augmentation of voluntary alcohol consumption in C57B1/6j but not in DBA/2j mice. Physiol Behav 1994;56:501–509.

    PubMed  CAS  Google Scholar 

  150. Sieck MH, Baumbach HD. Differential effects of peripheral and central anosmia producing techniques on spontaneous behavior patterns. Physiol Behav 1974;13:407–425.

    PubMed  CAS  Google Scholar 

  151. van Riezen H, Schnieden H, Wren AF. Olfactory bulb ablation in the rat: behavioural changes and their reversal by antidepressant drugs. Br J Pharmacol 1977;60:521–528.

    PubMed  Google Scholar 

  152. Grecksch G, Zhou D, Franke C, et al. Influence of olfactory bulbectomy and subsequent imipramine treatment on 5-hydroxytryptaminergic presynapses in the rat frontal cortex: behavioural correlates. Br J Pharmacol 1997;122:1725–1731.

    PubMed  CAS  Google Scholar 

  153. Norrholm SD, Ouimet CC. Altered dendritic spine density in animal models of depression and in response to antidepressant treatment. Synapse 2001;42:151–163.

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  155. Lynch MA, Leonard BE. Changes in brain gamma-aminobutyric acid concentrations following acute and chronic amphetamine administration and during post amphetamine depression. Biochem Pharmacol 1978;27:1853–1855.

    PubMed  CAS  Google Scholar 

  156. Gilliss B, Malanga CJ, Pieper JO, Carlezon WAJr. Cocaine and SKF-82958 potentiate brain stimulation reward in Swiss-Webster mice. Psychopharmacology (Berl) 2002;163:238–248.

    CAS  Google Scholar 

  157. Ikeda K, Moss SJ, Fowler SC, Niki H. Comparison of two intracranial self-stimulation (ICSS) paradigms in C57BL/6 mice: head-dipping and place-learning. Behav Brain Res 2001;126:49–56.

    PubMed  CAS  Google Scholar 

  158. Holmes A, Rodgers RJ. Influence of spatial and temporal manipulations on the anxiolytic efficacy of chlordiazepoxide in mice previously exposed to the elevated plus-maze. Neurosci Biobehav Rev 1999;23:971–980.

    PubMed  CAS  Google Scholar 

  159. Hogg S. A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav 1996;54:21–30.

    PubMed  CAS  Google Scholar 

  160. Crabbe JC, Wahlsten D, Dudek BC. Genetics of mouse behavior: interactions with laboratory environment. Science 1999;284:1670–1672.

    PubMed  CAS  Google Scholar 

  161. Wahlsten D, Metten P, Phillips TJ, et al. Different data from different labs: lessons from studies of gene-environment interaction. J Neurobiol 2003;54:283–311.

    PubMed  Google Scholar 

  162. Holmes A, Iles JP, Mayell SJ, Rodgers RJ. Prior test experience compromises the anxiolytic efficacy of chlordiazepoxide in the mouse light-dark exploration test. Behav Brain Res 2001;122:159–167.

    PubMed  CAS  Google Scholar 

  163. Holmes A, Rodgers RJ. Responses of Swiss-Webster mice to repeated plus-maze experience: further evidence for a qualitative shift in emotional state? Pharmacol Biochem Behav 1998;60:473–488.

    PubMed  CAS  Google Scholar 

  164. Schramm NL, McDonald MP, Limbird LE. The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety. J Neurosci 2001;21:4875–4882.

    PubMed  CAS  Google Scholar 

  165. Conti AC, Cryan JF, Dalvi A, Lucki I, Blendy JA. cAMP response element-binding protein is essential for the upregulation of brain-derived neurotrophic factor transcription, but not the behavioral or endocrine responses to antidepressant drugs. J Neurosci 2002;22:3262–3268.

    PubMed  CAS  Google Scholar 

  166. McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R. The use of behavioral test batteries: effects of training history. Physiol Behav 2001;73:705–717.

    PubMed  CAS  Google Scholar 

  167. Wahlsten D, Rustay NR, Metten P, Crabbe JC. In search of a better mouse test. Trends Neurosci 2003;26:132–136.

    PubMed  CAS  Google Scholar 

  168. Holmes A, Wrenn CC, Harris AP, Thayer KE, Crawley JN. Behavioral profiles of inbred strains on novel olfactory, spatial and emotional tests for reference memory in mice. Genes Brain Behav 2002;1:55–69.

    PubMed  CAS  Google Scholar 

  169. Rodgers RJ, Davies B, Shore R. Absence of anxiolytic response to chlordiazepoxide in two common background strains exposed to the elevated plus-maze: importance and implications of behavioural baseline. Genes Brain Behav 2002;1:242–251.

    PubMed  CAS  Google Scholar 

  170. Voikar V, Koks S, Vasar E, Rauvala H. Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies. Physiol Behav 2001;72:271–281.

    PubMed  CAS  Google Scholar 

  171. Cook MN, Bolivar VJ, McFadyen MP, Flaherty L. Behavioral differences among 129 substrains: implications for knockout and transgenic mice. Behav Neurosci 2002;116:600–611.

    PubMed  Google Scholar 

  172. Contet C, Rawlins JN, Deacon RM. A comparison of 129S2/SvHsd and C57BL/6JOlaHsd mice on a test battery assessing sensorimotor, affective and cognitive behaviours: implications for the study of genetically modified mice. Behav Brain Res 2001;124:33–46.

    PubMed  CAS  Google Scholar 

  173. Holmes A, Lit Q, Murphy DL, Gold E, Crawley JN. Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the influence of genetic background. Genes Brain Behav 2003;2:365–380.

    PubMed  CAS  Google Scholar 

  174. Nadeau JH. Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 2003;13:290–295.

    PubMed  CAS  Google Scholar 

  175. Hood HM, Belknap JK, Crabbe JC, Buck KJ. Genomewide search for epistasis in a complex trait: pentobarbital withdrawal convulsions in mice. Behav Genet 2001;31:93–100.

    PubMed  CAS  Google Scholar 

  176. Gerlai R. Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci 1996;19:177–181.

    PubMed  CAS  Google Scholar 

  177. Crawley JN, Belknap JK, Collins A, et al. Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology (Berl) 1997;132:107–124.

    CAS  Google Scholar 

  178. Wolfer DP, Crusio WE, Lipp HP. Knockout mice: simple solutions to the problems of genetic background and flanking genes. Trends Neurosci 2002;25:336–340.

    PubMed  CAS  Google Scholar 

  179. Wong GT. Speed congenics: applications for transgenic and knock-out mouse strains. Neuropeptides 2002;36:230–236.

    PubMed  CAS  Google Scholar 

  180. Meaney MJ. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 2001;24:1161–1192.

    PubMed  CAS  Google Scholar 

  181. Anisman H, Zaharia MD, Meaney MJ, Merali Z. Do early-life events permanently alter behavioral and hormonal responses to stressors? Int J Dev Neurosci 1998;16:149–164.

    PubMed  CAS  Google Scholar 

  182. Francis DD, Szegda K, Campbell G, Martin WD, Insel TR. Epigenetic sources of behavioral differences in mice. Nat Neurosci 2003;6:445–446.

    PubMed  CAS  Google Scholar 

  183. Bale TL, Picetti R, Contarino A, Koob GF, Vale WW, Lee KF. Mice deficient for both corti-cotropin-releasing factor receptor 1 (CRFR1) and CRFR2 have an impaired stress response and display sexually dichotomous anxiety-like behavior. J Neurosci 2002;22:193–199.

    PubMed  CAS  Google Scholar 

  184. Kendler KS. Twin studies of psychiatric illness: an update. Arch Gen Psychiatry 2001;58:1005–1014.

    PubMed  CAS  Google Scholar 

  185. Murphy DL, Uhl GR, Holmes A, et al. Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders. Genes Brain Behav 2003;2:350–364.

    PubMed  CAS  Google Scholar 

  186. Rutter M, Silberg J. Gene-environment interplay in relation to emotional and behavioral disturbance. Annu Rev Psychol 2002;53:463–490.

    PubMed  Google Scholar 

  187. McGuffin P, Riley B, Plomin R. Genomics and behavior. Toward behavioral genomics. Science 2001;291:1232–1249.

    PubMed  CAS  Google Scholar 

  188. Caspi A, McClay J, Moffitt TE, et al. Role of genotype in the cycle of violence in maltreated children. Science 2002;297:851–854.

    PubMed  CAS  Google Scholar 

  189. Caspi A, Sugden K, Moffitt TE, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003;301:386–389.

    PubMed  CAS  Google Scholar 

  190. Singer JB, Hill AE, Burrage LC, et al. Genetic dissection of complex traits with chromosome substitution strains of mice. Science 2004;304:445–448.

    PubMed  CAS  Google Scholar 

  191. Talbot CJ, Radcliffe RA, Fullerton J, Hitzemann R, Wehner JM, Flint J. Fine scale mapping of a genetic locus for conditioned fear. Mamm Genome 2003;14:223–230.

    PubMed  Google Scholar 

  192. Hommel JD, Sears RM, Georgescu D, Simmons DL, DiLeone RJ. Local gene knockdown in the brain using viral-mediated RNA interference. Nat Med 2003;9:1539–1544.

    PubMed  CAS  Google Scholar 

  193. El-Ghundi M, O’Dowd BF, Erclik M, George SR. Attenuation of sucrose reinforcement in dopamine D1 receptor deficient mice. Eur J Neurosci 2003;17:851–862.

    PubMed  Google Scholar 

  194. Dixon AK, Huber C, Lowe DA. Clozapine promotes approach-oriented behavior in male mice. J Clin Psychiatry 1994;55(Suppl B):4–7.

    PubMed  Google Scholar 

  195. Nonogaki K, Strack AM, Dallman MF, Tecott LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med 1998;4:1152–1156.

    PubMed  CAS  Google Scholar 

  196. Karolyi IJ, Burrows HL, Ramesh TM, et al. Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice. Proc Natl Acad Sci USA 1999;96:11,595–11,600.

    PubMed  CAS  Google Scholar 

  197. Boutrel B, Franc B, Hen R, Hamon M, Adrien J. Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced in 5-HT1B knock-out mice. J Neurosci 1999;19:3204–3212.

    PubMed  CAS  Google Scholar 

  198. Boutrel B, Monaca C, Hen R, Hamon M, Adrien J. Involvement of 5-HT1A receptors in homeo-static and stress-induced adaptive regulations of paradoxical sleep: studies in 5-HT1A knock-out mice. J Neurosci 2002;22:4686–4692.

    PubMed  CAS  Google Scholar 

  199. El Yacoubi M, Bouali S, Popa D, et al. Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression. Proc Natl Acad Sci USA 2003;100:6227–6232.

    PubMed  Google Scholar 

  200. Kafkafi N, Pagis M, Lipkind D, et al. Darting behavior: a quantitative movement pattern designed for discrimination and replicability in mouse locomotor behavior. Behav Brain Res 2003;142:193–205.

    PubMed  Google Scholar 

  201. Mizoguchi K, Yuzurihara M, Ishige A, Sasaki H, Tabira T. Chronic stress impairs rotarod performance in rats: implications for depressive state. Pharmacol Biochem Behav 2002;71:79–84.

    PubMed  CAS  Google Scholar 

  202. Nonogaki K, Abdallah L, Goulding EH, Bonasera SJ, Tecott LH. Hyperactivity and reduced energy cost of physical activity in serotonin 5-HT(2C) receptor mutant mice. Diabetes 2003;52:315–320.

    PubMed  CAS  Google Scholar 

  203. Grippo AJ, Beltz TG, Johnson AK. Behavioral and cardiovascular changes in the chronic mild stress model of depression. Physiol Behav 2003;78:703–710.

    PubMed  CAS  Google Scholar 

  204. Ballard TM, Pauly-Evers M, Higgins GA, et al. Severe impairment of NMDA receptor function in mice carrying targeted point mutations in the glycine binding site results in drug-resistant nonhabituating hyperactivity. J Neurosci 2002;22:6713–6723.

    PubMed  CAS  Google Scholar 

  205. Cheeta S, Ruigt G, van Proosdij J, Willner P. Changes in sleep architecture following chronic mild stress. Biol Psychiatry 1997;41:419–427.

    PubMed  CAS  Google Scholar 

  206. Estape N, Steckler T. Cholinergic blockade impairs performance in operant DNMTP in two inbred strains of mice. Pharmacol Biochem Behav 2002;72:319–334.

    PubMed  CAS  Google Scholar 

  207. Contarino A, Dellu F, Koob GF, et al. Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1. Brain Res 1999;835:1–9.

    PubMed  CAS  Google Scholar 

  208. van Gaalen MM, Stenzel-Poore M, Holsboer F, Steckler T. Reduced attention in mice overproducing corticotropin-releasing hormone. Behav Brain Res 2003;142:69–79.

    PubMed  Google Scholar 

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Authors
  1. Andrew Holmes
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  2. John F. Cryan
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Editors and Affiliations

  1. Department of Statistics, Yeshiva University, New York, NY

    Gene S. Fisch PhD

  2. Department of Psychology, CUNY/Lehman College, New York, NY

    Gene S. Fisch PhD

  3. Wellcome Trust Centre for Human Genetics, Oxford, UK

    Jonathan Flint MD, MRCPsych

  4. Department of Psychiatry, University of Oxford, Oxford, UK

    Jonathan Flint MD, MRCPsych

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Holmes, A., Cryan, J.F. (2006). Modeling Human Anxiety and Depression in Mutant Mice. In: Fisch, G.S., Flint, J. (eds) Transgenic and Knockout Models of Neuropsychiatric Disorders. Contemporary Clinical Neuroscience. Humana Press. https://doi.org/10.1007/978-1-59745-058-4_12

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