Abstract
Preclinical animal models have supported much of the recent rapid expansion of neuroscience research and have facilitated critical discoveries that undoubtedly benefit patients suffering from psychiatric disorders. This overview serves as an introduction for the following chapters describing both in vivo and in vitro preclinical models of psychiatric disease components and briefly describes models related to drug dependence and affective disorders. Although there are no perfect animal models of any psychiatric disorder, models do exist for many elements of each disease state or stage. In many cases, the development of certain models is essentially restricted to the human clinical laboratory domain for the purpose of maximizing validity, whereas the use of in vitro models may best represent an adjunctive, well-controlled means to model specific signaling mechanisms associated with psychiatric disease states. The data generated by preclinical models are only as valid as the model itself, and the development and refinement of animal models for human psychiatric disorders continues to be an important challenge. Collaborative relationships between basic neuroscience and clinical modeling could greatly benefit the development of new and better models, in addition to facilitating medications development.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Edwards, S., and Koob, G. F. (2010) Neurobiology of dysregulated motivational systems in drug addiction, Future Neurol 5, 393–401.
Covington, H. E., 3rd, Vialou, V., and Nestler, E. J. (2010) From synapse to nucleus: novel targets for treating depression, Neuropharmacology 58, 683–693.
McKinney, W. (1989) Basis of development of animal models in psychiatry: an overview. in Animal models of depression (Koob, G. F., Ehlers CL, Kupfer DJ, Ed.), pp 3–17, Birkhauser, Boston, Basel.
Adriani, W., Granstrem, O., Macri, S., Izykenova, G., Dambinova, S., and Laviola, G. (2004) Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine, Neuropsychopharmacology 29, 869–878.
Brown, S. A., and Tapert, S. F. (2004) Adolescence and the trajectory of alcohol use: basic to clinical studies, Ann N Y Acad Sci 1021, 234–244.
O’Dell, L. E. (2009) A psychobiological framework of the substrates that mediate nicotine use during adolescence, Neuropharmacology 56 Suppl 1, 263–278.
Schramm-Sapyta, N. L., Walker, Q. D., Caster, J. M., Levin, E. D., and Kuhn, C. M. (2009) Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models, Psychopharmacology (Berl) 206, 1–21.
Palanza, P. (2001) Animal models of anxiety and depression: how are females different?, Neurosci Biobehav Rev 25, 219–233.
Fattore, L., Altea, S., and Fratta, W. (2008) Sex differences in drug addiction: a review of animal and human studies, Womens Health (Lond Engl) 4, 51–65.
McClung, C. A. (2007) Circadian genes, rhythms and the biology of mood disorders, Pharmacol Ther 114, 222–232.
Falcon, E., and McClung, C. A. (2009) A role for the circadian genes in drug addiction, Neuropharmacology 56 Suppl 1, 91–96.
Ebel, R. (1961) Must all tests be valid?, American Psychologist 16, 640–647.
Sayette, M. A., Shiffman, S., Tiffany, S. T., Niaura, R. S., Martin, C. S., and Shadel, W. G. (2000) The measurement of drug craving, Addiction 95 Suppl 2, S189–210.
Cronbach, L. J., and Meehl, P. E. (1955) Construct validity in psychological tests, Psychol Bull 52, 281–302.
Katz, J. L., and Higgins, S. T. (2003) The validity of the reinstatement model of craving and relapse to drug use, Psychopharmacology (Berl) 168, 21–30.
McKinney, W. (1988) Models of Mental Disorders: A New Comparative Psychiatry, Plenum, New York.
MA Geyer, A. M. (1995) Animal models of psychiatric disorders, in Psychopharmacology: The Fourth Generation of Progress (FE Bloom, D. K., Ed.), pp 787–798 Raven Press, New York.
Willner, P. (1984) The validity of animal models of depression, Psychopharmacology (Berl) 83, 1–16.
Matthysse, S. (1986) Animal models in psychiatric research, Prog Brain Res 65, 259–270.
Ellenbroek, B. A., and Cools, A. R. (2000) Animal models for the negative symptoms of schizophrenia, Behav Pharmacol 11, 223–233.
Markou, A., and Koob, G. F. (1992) Construct validity of a self-stimulation threshold paradigm: effects of reward and performance manipulations, Physiol Behav 51, 111–119.
Gilpin, N. W., and Koob, G. F. (2008) Neurobiology of Alcohol Dependence: Focus on Motivational Mechanisms, Alcohol Res Health 31, 185–195.
Association, A. P. (1994) Diagnostic and Statistical Manual of Mental Disorders, 4 ed.
Koob, G. F., and Le Moal, M. (2001) Drug addiction, dysregulation of reward, and allostasis, Neuropsychopharmacology 24, 97–129.
Bindra (1976) A Theory of Intelligent Behavior, Wiley, New York.
Koob, G. F. (2008) A role for brain stress systems in addiction, Neuron 59, 11–34.
Shippenberg TS, G. K. (2002) Recent advances in animal models of drug addiction and alcoholism, in Neuropsychopharmacology: The Fifth Generation of Progress (KL Davis, D. C., JT Coyle, C Nemeroff, Ed.), pp 1381–1397, Lippincott Williams and Wilkins, Philadelphia.
Carlezon, W. A., Jr., and Chartoff, E. H. (2007) Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation, Nat Protoc 2, 2987–2995.
Ahmed, S. H., and Koob, G. F. (1998) Transition from moderate to excessive drug intake: change in hedonic set point, Science 282, 298–300.
Ahmed, S. H., Walker, J. R., and Koob, G. F. (2000) Persistent increase in the motivation to take heroin in rats with a history of drug escalation, Neuropsychopharmacology 22, 413–421.
Roberts, A. J., Heyser, C. J., Cole, M., Griffin, P., and Koob, G. F. (2000) Excessive ethanol drinking following a history of dependence: animal model of allostasis, Neuropsychopharmacology 22, 581–594.
Breese, G. R., Chu, K., Dayas, C. V., Funk, D., Knapp, D. J., Koob, G. F., Le, D. A., O’Dell, L. E., Overstreet, D. H., Roberts, A. J., Sinha, R., Valdez, G. R., and Weiss, F. (2005) Stress enhancement of craving during sobriety: a risk for relapse, Alcohol Clin Exp Res 29, 185–195.
Kitamura, O., Wee, S., Specio, S. E., Koob, G. F., and Pulvirenti, L. (2006) Escalation of methamphetamine self-administration in rats: a dose-effect function, Psychopharmacology (Berl) 186, 48–53.
O’Dell, L. E., Chen, S. A., Smith, R. T., Specio, S. E., Balster, R. L., Paterson, N. E., Markou, A., Zorrilla, E. P., and Koob, G. F. (2007) Extended access to nicotine self-administration leads to dependence: Circadian measures, withdrawal measures, and extinction behavior in rats, J Pharmacol Exp Ther 320, 180–193.
Edwards, S., Graham, D. L., Bachtell, R. K., and Self, D. W. (2007) Region-specific tolerance to cocaine-regulated cAMP-dependent protein phosphorylation following chronic self-administration, Eur J Neurosci 25, 2201–2213.
Self, D. W. (1998) Neural substrates of drug craving and relapse in drug addiction, Ann Med 30, 379–389.
Shaham, Y., Shalev, U., Lu, L., De Wit, H., and Stewart, J. (2003) The reinstatement model of drug relapse: history, methodology and major findings, Psychopharmacology (Berl) 168, 3–20.
Miczek, K. A., Yap, J. J., and Covington, H. E., 3rd. (2008) Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake, Pharmacol Ther 120, 102–128.
Callahan, L. B., Tschetter, K. E., and Ronan, P. J. (2007) Difficulties associated with the cocaine conditioned place preference (CPP) test using rats, in Society for Neuroscience Abstracts, San Diego.
Markou, A., Weiss, F., Gold, L. H., Caine, S. B., Schulteis, G., and Koob, G. F. (1993) Animal models of drug craving, Psychopharmacology (Berl) 112, 163–182.
Tiffany, S. T., Carter, B. L., and Singleton, E. G. (2000) Challenges in the manipulation, assessment and interpretation of craving relevant variables, Addiction 95 Suppl 2, S177–187.
JF Cryan, C. S., TG Dinan, F Borsini. (2008) Developing more efficacious antidepressant medication: improving and aligning preclinical and clinical assessment tools. in Animal and Translational Models for CNS Drug Discovery (RA McArthur, F Borsini, Ed.), Elsevier, Amsterdam.
Levinson, D. F. (2006) The genetics of depression: a review, Biol Psychiatry 60, 84–92.
Krishnan, V., and Nestler, E. J. (2008) The molecular neurobiology of depression, Nature 455, 894–902.
Wurtman, R. J. (2005) Genes, stress, and depression, Metabolism 54, 16–19.
Moller, H. J. (2003) Suicide, suicidality and suicide prevention in affective disorders, Acta Psychiatr Scand Suppl, 73–80.
Moreau, J. L. (1997) Reliable monitoring of hedonic deficits in the chronic mild stress model of depression, Psychopharmacology (Berl) 134, 357–358; discussion 371–357.
Willner, P., Towell, A., Sampson, D., Sophokleous, S., and Muscat, R. (1987) Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant, Psychopharmacology (Berl) 93, 358–364.
Yu, J., Liu, Q., Wang, Y. Q., Wang, J., Li, X. Y., Cao, X. D., and Wu, G. C. (2007) Electroacupuncture combined with clomipramine enhances antidepressant effect in rodents, Neurosci Lett 421, 5–9.
Reid, I., Forbes, N., Stewart, C., and Matthews, K. (1997) Chronic mild stress and depressive disorder: a useful new model?, Psychopharmacology (Berl) 134, 365–367; discussion 371–367.
Muscat, R., Kyprianou, T., Osman, M., Phillips, G., and Willner, P. (1991) Sweetness-dependent facilitation of sucrose drinking by raclopride is unrelated to calorie content, Pharmacol Biochem Behav 40, 209–213.
Willner, P., Muscat, R., and Papp, M. (1992) Chronic mild stress-induced anhedonia: a realistic animal model of depression, Neurosci Biobehav Rev 16, 525–534.
Muscat, R., and Willner, P. (1992) Suppression of sucrose drinking by chronic mild unpredictable stress: a methodological analysis, Neurosci Biobehav Rev 16, 507–517.
Katz, R. J. (1982) Animal model of depression: pharmacological sensitivity of a hedonic deficit, Pharmacol Biochem Behav 16, 965–968.
Von Frijtag, J. C., Van den Bos, R., and Spruijt, B. M. (2002) Imipramine restores the long-term impairment of appetitive behavior in socially stressed rats, Psychopharmacology (Berl) 162, 232–238.
Duncko, R., Schwendt, M., and Jezova, D. (2003) Altered glutamate receptor and corticoliberin gene expression in brain regions related to hedonic behavior in rats, Pharmacol Biochem Behav 76, 9–16.
Cheeta, S., Broekkamp, C., and Willner, P. (1994) Stereospecific reversal of stress-induced anhedonia by mianserin and its (+)-enantiomer, Psychopharmacology (Berl) 116, 523–528.
Rygula, R., Abumaria, N., Domenici, E., Hiemke, C., and Fuchs, E. (2006) Effects of fluoxetine on behavioral deficits evoked by chronic social stress in rats, Behav Brain Res 174, 188–192.
Rygula, R., Abumaria, N., Flugge, G., Hiemke, C., Fuchs, E., Ruther, E., and Havemann-Reinecke, U. (2006) Citalopram counteracts depressive-like symptoms evoked by chronic social stress in rats, Behav Pharmacol 17, 19–29.
Casarotto, P. C., and Andreatini, R. (2007) Repeated paroxetine treatment reverses anhedonia induced in rats by chronic mild stress or dexamethasone, Eur Neuropsychopharmacol 17, 735–742.
Markou, A., and Koob, G. F. (1991) Postcocaine anhedonia. An animal model of cocaine withdrawal, Neuropsychopharmacology 4, 17–26.
I Geller, J. S. (1960) The effect of meprobamate, barbiturates, d-amphetamine and promazine on experimentally-induced conflict in the rat, Psychopharmacologia 1, 482–491.
File, S. E., and Hyde, J. R. (1978) Can social interaction be used to measure anxiety?, Br J Pharmacol 62, 19–24.
Archer, J. (1973) Tests for emotionality in rats and mice: a review, Anim Behav 21, 205–235.
Dawson, G. R., and Tricklebank, M. D. (1995) Use of the elevated plus maze in the search for novel anxiolytic agents, Trends Pharmacol Sci 16, 33–36.
Handley, S. L., and Mithani, S. (1984) Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of ‘fear’-motivated behaviour, Naunyn Schmiedebergs Arch Pharmacol 327, 1–5.
Pellow, S., Chopin, P., File, S. E., and Briley, M. (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat, J Neurosci Methods 14, 149–167.
Pellow, S., and File, S. E. (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat, Pharmacol Biochem Behav 24, 525–529.
Handley, S. L., and McBlane, J. W. (1993) An assessment of the elevated X-maze for studying anxiety and anxiety-modulating drugs, J Pharmacol Toxicol Methods 29, 129–138.
M Reibaud, A. B. (1993) Evolution of putative anxiolytics in the elevated plus-maze, in Paradigms for the Study of Behavior (Conn, M., Ed.), pp 230–239, Academic Press, San Diego.
Gorman, A. L., and Dunn, A. J. (1993) Beta-adrenergic receptors are involved in stress-related behavioral changes, Pharmacol Biochem Behav 45, 1–7.
JS Andrews, C. B. (1993) Procedures to identify anxiolytic or anxiogenic agents, in Behavioral Neuroscience: A Practical Approach (Sahgal, A., Ed.), pp 37–54, IRL Press, Oxford.
Korte, S. M., Korte-Bouws, G. A., Bohus, B., and Koob, G. F. (1994) Effect of corticotropin-releasing factor antagonist on behavioral and neuroendocrine responses during exposure to defensive burying paradigm in rats, Physiol Behav 56, 115–120.
Bowers, R. L., Herzog, C. D., Stone, E. H., and Dionne, T. J. (1992) Defensive burying following injections of cholecystokinin, bombesin, and LiCl in rats, Physiol Behav 51, 969–972.
Korte, S. M., and Bohus, B. (1990) The effect of ipsapirone on behavioural and cardiac responses in the shock-probe/defensive burying test in male rats, Eur J Pharmacol 181, 307–310.
CL Broekkamp, F. J. (1989) The relationship between various animal models of anxiety, fear-related psychiatric symptoms and response to serotonergic drugs, in Behavioral Pharmacology of 5-HT (P Bevan, R. C., T Archer, Ed.), pp 321–325, Erlbaum, Hillsdale.
Feder, A., Nestler, E. J., and Charney, D. S. (2009) Psychobiology and molecular genetics of resilience, Nat Rev Neurosci 10, 446–457.
Harro, J. (2010) Inter-individual differences in neurobiology as vulnerability factors for affective disorders: implications for psychopharmacology, Pharmacol Ther 125, 402–422.
Litt, M. D., and Cooney, N. L. (1999) Inducing craving for alcohol in the laboratory, Alcohol Res Health 23, 174–178.
Mason, B. J., Light, J. M., Williams, L. D., and Drobes, D. J. (2009) Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin, Addict Biol 14, 73–83.
Epstein, D. H., and Preston, K. L. (2003) The reinstatement model and relapse prevention: a clinical perspective, Psychopharmacology (Berl) 168, 31–41.
Koob, G. F., Kenneth Lloyd, G., and Mason, B. J. (2009) Development of pharmacotherapies for drug addiction: a Rosetta stone approach, Nat Rev Drug Discov 8, 500–515.
GA Marlatt, J. G. (1985) Relapse Prevention, Guilford Press, New York.
Mason, B. J., Light, J. M., Escher, T., and Drobes, D. J. (2008) Effect of positive and negative affective stimuli and beverage cues on measures of craving in non treatment-seeking alcoholics, Psychopharmacology (Berl) 200, 141–150.
Nestler, E. J., Barrot, M., and Self, D. W. (2001) DeltaFosB: a sustained molecular switch for addiction, Proc Natl Acad Sci USA 98, 11042–11046.
Ulery, P. G., Rudenko, G., and Nestler, E. J. (2006) Regulation of DeltaFosB stability by phosphorylation, J Neurosci 26, 5131–5142.
Carle, T. L., Ohnishi, Y. N., Ohnishi, Y. H., Alibhai, I. N., Wilkinson, M. B., Kumar, A., and Nestler, E. J. (2007) Proteasome-dependent and -independent mechanisms for FosB destabilization: identification of FosB degron domains and implications for DeltaFosB stability, Eur J Neurosci 25, 3009–3019.
Alibhai, I. N., Green, T. A., Potashkin, J. A., and Nestler, E. J. (2007) Regulation of fosB and DeltafosB mRNA expression: in vivo and in vitro studies, Brain Res 1143, 22–33.
Ulery-Reynolds, P. G., Castillo, M. A., Vialou, V., Russo, S. J., and Nestler, E. J. (2009) Phosphorylation of DeltaFosB mediates its stability in vivo, Neuroscience 158, 369–372.
Harris, R. A., Trudell, J. R., and Mihic, S. J. (2008) Ethanol’s molecular targets, Sci Signal 1, re7.
Martini, L., and Whistler, J. L. (2007) The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence, Curr Opin Neurobiol 17, 556–564.
Berger, A. C., and Whistler, J. L. (2010) How to design an opioid drug that causes reduced tolerance and dependence, Ann Neurol 67, 559–569.
Littleton, J. (2007) Acamprosate in Alcohol Dependence: Implications of a Unique Mechanism of Action, Journal of Addiction Medicine 1, 115–125.
Hollenbeck, P. J., and Bamburg, J. R. (2003) Comparing the properties of neuronal culture systems: a shopping guide for the cell biologist, Methods Cell Biol 71, 1–16.
Matteoli, M., Verderio, C., Krawzeski, K., Mundigl, O., Coco, S., Fumagalli, G., and De Camilli, P. (1995) Mechanisms of synaptogenesis in hippocampal neurons in primary culture, J Physiol Paris 89, 51–55.
Gao, C., and Wolf, M. E. (2007) Dopamine alters AMPA receptor synaptic expression and subunit composition in dopamine neurons of the ventral tegmental area cultured with prefrontal cortex neurons, J Neurosci 27, 14275–14285.
Fitzgerald, L. W., Ortiz, J., Hamedani, A. G., and Nestler, E. J. (1996) Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: common adaptations among cross-sensitizing agents, J Neurosci 16, 274–282.
Wolf, M. E. (1998) The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants, Prog Neurobiol 54, 679–720.
Saal, D., Dong, Y., Bonci, A., and Malenka, R. C. (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons, Neuron 37, 577–582.
Acknowledgments
The authors would like to thank Michael Arends for editorial assistance. This is publication number 20895 from The Scripps Research Institute. Preparation of this chapter was funded by the Pearson Center for Alcoholism and Addiction Research and National Institutes of Health grants AA018250, AA06420, AA12602, and AA08459 from the National Institute on Alcohol Abuse and Alcoholism, DA04043, DA04398, and DA023597 from the National Institute on Drug Abuse, and DK26742 from the National Institute of Diabetes and Digestive and Kidney Diseases.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Edwards, S., Koob, G.F. (2012). Experimental Psychiatric Illness and Drug Abuse Models: From Human to Animal, an Overview. In: Kobeissy, F. (eds) Psychiatric Disorders. Methods in Molecular Biology, vol 829. Humana Press. https://doi.org/10.1007/978-1-61779-458-2_2
Download citation
DOI: https://doi.org/10.1007/978-1-61779-458-2_2
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-457-5
Online ISBN: 978-1-61779-458-2
eBook Packages: Springer Protocols