Does anyone know about some animal models, preferably using rodents, for the study of this disease?
Dear Dr Nahata,
There are two models, pharmacological and lesion models. You can use rats and mice with this purpose. I recommend you these links
With best regards
http://en.wikipedia.org/wiki/Animal_models_of_schizophrenia
https://www.google.com.co/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&cad=rja&ved=0CEIQFjAC&url=http%3A%2F%2Fdownloads.hindawi.com%2Fjournals%2Fnp%2F2012%2F832757.pdf&ei=KD0kUaKICY2W8gSzroG4DQ&usg=AFQjCNElEcCzlg1xHjmWNy4uEQyevCcwcw&bvm=bv.42661473,d.eWU
http://schizophreniabulletin.oxfordjournals.org/content/36/6/1066.full.pdf
http://db.wdc-jp.com/cgi-bin/psj/data/bpb/pdf/201109/b09_1358.pdf
http://speapsl.aphp.fr/publications/2007/2007-8.pdf
http://db.wdc-jp.com/cgi-bin/psj/data/bpb/pdf/201109/b09_1358.pdf
Dear Dr Nahata,
There are two models, pharmacological and lesion models. You can use rats and mice with this purpose. I recommend you these links
With best regards
http://en.wikipedia.org/wiki/Animal_models_of_schizophrenia
https://www.google.com.co/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&cad=rja&ved=0CEIQFjAC&url=http%3A%2F%2Fdownloads.hindawi.com%2Fjournals%2Fnp%2F2012%2F832757.pdf&ei=KD0kUaKICY2W8gSzroG4DQ&usg=AFQjCNElEcCzlg1xHjmWNy4uEQyevCcwcw&bvm=bv.42661473,d.eWU
http://schizophreniabulletin.oxfordjournals.org/content/36/6/1066.full.pdf
http://db.wdc-jp.com/cgi-bin/psj/data/bpb/pdf/201109/b09_1358.pdf
http://speapsl.aphp.fr/publications/2007/2007-8.pdf
http://db.wdc-jp.com/cgi-bin/psj/data/bpb/pdf/201109/b09_1358.pdf
This is other link that can be useful. With best regards
http://faculty.psy.ohio-state.edu/bruno/PDF%20files/Schizophrenia%20from%20phenomenology%20to%20neurobiology.pdf
Hi Alok,
Here are 13 papers on schizophrenia animal models using rodents.
Good luck!
Pharmacol Ther. 2012 Jan;133(1):19-25. doi: 10.1016/j.pharmthera.2011.07.005. Epub 2011 Aug 3.
Cortical disinhibition in the neonatal ventral hippocampal lesion model of schizophrenia: new vistas on possible therapeutic approaches.
O'Donnell P.
Source
Department of Anatomy & Neurobiology, Department of Psychiatry, University of Maryland School of Medicine, United States. [email protected]
Abstract
The neonatal ventral hippocampal lesion (NVHL) model of schizophrenia has been extensively used in many laboratories over the past couple of decades. With more than 120 publications from over 15 research groups, this developmental model yields a number of schizophrenia-relevant behavioral, neurochemical and electrophysiological deficits. An important aspect of this model is the delayed emergence of alterations, typically during adolescence despite the manipulation that causes them having been performed during the first postnatal week. Such delayed timing reflects the periadolescent onset of schizophrenia symptoms and may be related to the protracted maturation of cortical circuits, affected in both the disease and the NVHL model. Here, I will review the work we have done regarding the maturation of prefrontal cortical-accumbens circuits during adolescence, and how this maturation is affected in rats with a NVHL. One of the principal elements affected in NVHL rats is the dopamine modulation of prefrontal cortical interneurons, and this finding is convergent with data from many other developmental, genetic and pharmacological models. An altered maturation of interneuron function would yield a disinhibited cortex, and this opens the way to novel therapeutic approaches for treatment and even prevention of schizophrenia.
Copyright © 2011 Elsevier Inc. All rights reserved.
PMID: 21839776 [PubMed - indexed for MEDLINE]
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2.
Neuroscience. 2012 Jun 1;211:136-64. doi: 10.1016/j.neuroscience.2011.07.051. Epub 2011 Jul 27.
Avoiding mouse traps in schizophrenia genetics: lessons and promises from current and emerging mouse models.
Kvajo M, McKellar H, Gogos JA.
Source
Department of Physiology and Cellular Biophysics, College of Physicians & Surgeons, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
Abstract
Schizophrenia is one of the most common psychiatric disorders, but despite progress in identifying the genetic factors implicated in its development, the mechanisms underlying its etiology and pathogenesis remain poorly understood. Development of mouse models is critical for expanding our understanding of the causes of schizophrenia. However, translation of disease pathology into mouse models has proven to be challenging, primarily due to the complex genetic architecture of schizophrenia and the difficulties in the re-creation of susceptibility alleles in the mouse genome. In this review we highlight current research on models of major susceptibility loci and the information accrued from their analysis. We describe and compare the different approaches that are necessitated by diverse susceptibility alleles, and discuss their advantages and drawbacks. Finally, we discuss emerging mouse models, such as second-generation pathophysiology models based on innovative approaches that are facilitated by the information gathered from the current genetic mouse models.
Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
PMID: 21821099 [PubMed - indexed for MEDLINE] PMCID: PMC3351555 [Available on 2013/6/1]
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3.
Schizophr Bull. 2010 Nov;36(6):1066-72. doi: 10.1093/schbul/sbq106. Epub 2010 Sep 24.
The role of rodent models in the discovery of new treatments for schizophrenia: updating our strategy.
Moore H.
Source
Department of Integrative Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, Mail Unit 14, New York, NY 10032, USA. [email protected]
Abstract
The strategies used in preclinical research in schizophrenia have evolved from experiments focused on the pharmacology of existing antipsychotic or psychotomimetic drugs to the broader study of pharmacological modulation of the neurobehavioral systems affected in schizophrenia. As an additional approach, neurodevelopmental, including genetic, manipulations have become increasingly used to model disease risk factors or to induce schizophrenia-relevant neuropathology. In the vast majority of these models, behavioral testing paradigms are used to test the effects of the drugs or developmental manipulations on psychomotor, cognitive and affective processes hypothesized to be affected in schizophrenia. The term "animal model of schizophrenia" is now applied to any combination of these strategies. The expansion in animal modeling strategies has led to significant innovation in identifying novel neural mechanisms that may contribute not only to psychosis but also to the cognitive and negative symptoms of schizophrenia. Yet one cost of innovation in the discovery of truly novel treatment targets is a higher risk for false positives--drugs that have shown promise in animal models but not in clinical trials. The goals of this commentary are to first provide a brief history and conceptualization of rodent models in preclinical research and then examine the issues to be addressed in order to increase the predictive power of animal models in the identification of new treatment targets and, ultimately, new effective treatments for schizophrenia.
PMID: 20870929 [PubMed - indexed for MEDLINE] PMCID: PMC2963052 Free PMC Article
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4.
Physiol Res. 2010;59(5):811-9. Epub 2010 Apr 20.
Pain perception in neurodevelopmental animal models of schizophrenia.
Franěk M, Vaculín S, Yamamotová A, Stastný F, Bubeníková-Valešová V, Rokyta R.
Source
Charles University in Prague, Third Medical Faculty, Department of Normal, Pathological and Clinical Physiology, Prague Psychiatric Center, Prague, Czech Republic. [email protected]
Abstract
Animal models are important for the investigation of mechanisms and therapeutic approaches in various human diseases, including schizophrenia. Recently, two neurodevelopmental rat models of this psychosis were developed based upon the use of subunit selective N-methyl-D-aspartate receptor agonists--quinolinic acid (QUIN) and N-acetyl-aspartyl-glutamate (NAAG). The aim of this study was to evaluate pain perception in these models. QUIN or NAAG was infused into lateral cerebral ventricles neonatally. In the adulthood, the pain perception was examined. The rats with neonatal brain lesions did not show any significant differences in acute mechanical nociception and in formalin test compared to controls. However, the neonatally lesioned rats exhibited significantly higher pain thresholds in thermal nociception. Increased levels of mechanical hyperalgesia, accompanying the sciatic nerve constriction (neuropathic pain), were also observed in lesioned rats. Although hyperalgesia was more pronounced in QUIN-treated animals, the number of c-Fos-immunoreactive neurons of the lumbar spinal cord was similar in experimental and control rats. We conclude that neonatal brain lesions attenuated the thermal perception in both nociceptive and neuropathic pain whereas mechanical pain was increased in the model of neuropathic pain only. Thus, nociceptive and neuropathic pain belongs--in addition to behavioral changes--among the parameters which are affected in described animal models of schizophrenia.
PMID: 20406041 [PubMed - indexed for MEDLINE] Free full text
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5.
Mol Psychiatry. 2010 Oct;15(10):987-95. doi: 10.1038/mp.2010.1. Epub 2010 Feb 2.
Novel animal models for studying complex brain disorders: BAC-driven miRNA-mediated in vivo silencing of gene expression.
Garbett KA, Horváth S, Ebert PJ, Schmidt MJ, Lwin K, Mitchell A, Levitt P, Mirnics K.
Source
Department of Psychiatry, Vanderbilt University, Nashville, TN 37232,USA.
Abstract
In schizophrenia, glutamic acid decarboxylase 1 (GAD1) disturbances are robust, consistently observed, cell-type specific and represent a core feature of the disease. In addition, neuropeptide Y (NPY), which is a phenotypic marker of a sub-population of GAD1-containing interneurons, has shown reduced expression in the prefrontal cortex in subjects with schizophrenia, suggesting that dysfunction of the NPY+ cortical interneuronal sub-population might be a core feature of this devastating disorder. However, modeling gene expression disturbances in schizophrenia in a cell type-specific manner has been extremely challenging. To more closely mimic these molecular and cellular human post-mortem findings, we generated a transgenic mouse in which we downregulated GAD1 mRNA expression specifically in NPY+ neurons. This novel, cell type-specific in vivo system for reducing gene expression uses a bacterial artificial chromosome (BAC) containing the NPY promoter-enhancer elements, the reporter molecule (eGFP) and a modified intron containing a synthetic microRNA (miRNA) targeted to GAD1. The animals of isogenic strains are generated rapidly, providing a new tool for better understanding the molecular disturbances in the GABAergic system observed in complex neuropsychiatric disorders such as schizophrenia. In the future, because of the small size of the silencing miRNAs combined with our BAC strategy, this method may be modified to allow generation of mice with simultaneous silencing of multiple genes in the same cells with a single construct, and production of splice-variant-specific knockdown animals.
PMID: 20125089 [PubMed - indexed for MEDLINE] PMCID: PMC3011211 Free PMC Article
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6.
Neurosci Biobehav Rev. 2010 Mar;34(3):285-94. doi: 10.1016/j.neubiorev.2009.07.010. Epub 2009 Aug 3.
Mice with genetically altered glutamate receptors as models of schizophrenia: a comprehensive review.
Inta D, Monyer H, Sprengel R, Meyer-Lindenberg A, Gass P.
Source
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, 68159 Mannheim, Germany. [email protected]
Abstract
Recent clinical evidence for the effectiveness of new antipsychotic drugs that specifically target glutamate receptors has rekindled interest in the glutamatergic system regarding pathophysiology and treatment of schizophrenia. The glutamatergic hypothesis of schizophrenia was triggered by the clinical/behavioural observation that NMDA receptor antagonists can induce psychosis in humans and abnormal behaviour with schizophrenia-like symptoms in animals. Initial models focused on NMDA receptor hypofunction as a potential pathogenetic mechanism. More recent genetic and pharmacological studies revealed that malfunction of other components of the glutamatergic system might also be relevant in explaining specific symptoms of this complex disease. Here, we review mutant mouse models with relevance for schizophrenia. These rodent models, in which specific glutamate receptor subtypes or various components of their intracellular transduction machinery are genetically altered, permit a detailed dissection of the contribution of different components of the glutamate system in inducing schizophrenia-like behaviours. They may provide insight into the pathophysiology of schizophrenia and prove useful in the development of new therapeutics.
(c) 2009 Elsevier Ltd. All rights reserved.
PMID: 19651155 [PubMed - indexed for MEDLINE]
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7.
J Psychopharmacol. 2010 Mar;24(3):407-19. doi: 10.1177/0269881108098787. Epub 2009 Feb 9.
Further neurochemical and behavioural investigation of Brattleboro rats as a putative model of schizophrenia.
Cilia J, Gartlon JE, Shilliam C, Dawson LA, Moore SH, Jones DN.
Source
Department of Biology, New Frontiers Science Park, GlaxoSmithKline plc, Harlow, Essex, UK.
Abstract
Brattleboro (BRAT) rats are a mutant variant of the Long-Evans (LE) strain deficient in the neurohormone vasopressin. BRAT rats show behavioural alterations relevant to schizophrenia. In particular, BRAT rats show deficits in prepulse inhibition (PPI) and alterations in various measures of cognition. The aim of this study was to replicate the reported PPI deficits in BRAT rats and its reversal by antipsychotic drugs and to investigate other behavioural and neurochemical characteristics. Acoustic startle reactivity, PPI, spontaneous and amphetamine-induced locomotor activity (LMA) and ex-vivo steady state neurochemistry were measured in male homozygous BRAT rats and LE rats. The effects of antipsychotics on PPI deficits were also determined. Relative to LE, BRAT rats showed enhanced startle reactivity, hyperactivity to a novel environment, PPI deficits and decreased levels of dopamine and DOPAC (dihydroxyphenylacetic acid) in the frontal cortex. BRAT and LE rats showed similar levels of hyperactivity following amphetamine (0.26 mg/kg s.c.). PPI deficits were attenuated by acute clozapine (5-10 mg/kg s.c.), risperidone (0.1-1 mg/kg i.p.), haloperidol (0.1-0.5 mg/kg p.o.) and less robustly by olanzapine (0.3-3 mg/kg s.c.). Chronic administration of clozapine (5 mg/kg s.c., once daily) attenuated baseline hyperactivity and elevated PPI of both strains. Clozapine concentrations were higher in BRAT brains compared with LE rats. These data confirm the reported PPI deficit in BRAT rats and its reversal by antipsychotic drugs, suggesting BRAT rats may represent a potential model for identifying novel antipsychotic drugs.
PMID: 19204063 [PubMed - indexed for MEDLINE]
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8.
Prog Brain Res. 2009;179:75-86. doi: 10.1016/S0079-6123(09)17909-8. Epub 2009 Nov 20.
Gene models of schizophrenia: DISC1 mouse models.
Jaaro-Peled H.
Source
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected]
Abstract
Disrupted in Schizophrenia-1 (DISC1) is one of the most likely susceptibility genes for schizophrenia (SZ). DISC1 is being established as a hub protein with various functions in the pre- and postnatal development of the nervous system. Since generation of a knockout (KO) mouse has proved challenging, various alternative approaches have been taken. Seven DISC1 mouse models have been described to date. All of them display neuroanatomical and behavioral abnormalities relevant to SZ, although most of them have not been fully characterized yet, requiring further analysis. NRG1 and ErbB4, also highly promising susceptibility genes for SZ, share many features with DISC1. They are involved in various aspects of pre- and postnatal neurodevelopment. The NRG1 and ErbB4 mouse models also display neuroanatomical and behavioral abnormalities similar to the DISC1 mouse models. In the future, four main directions need further study. First, further characterization of the seven DISC1 mouse models, especially in light of basic research findings. Second, more extensive employment of the inducible models. Third, generation of a DISC1 KO. Fourth, combination of the DISC1 mouse models with other risk factors: crossing with other genetic models such as NRG1/ErbB4 mutants and exposure to environmental risk factors.
2009 Elsevier B.V. All rights reserved.
PMID: 20302820 [PubMed - indexed for MEDLINE]
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9.
Prog Brain Res. 2009;179:35-47. doi: 10.1016/S0079-6123(09)17905-0. Epub 2009 Nov 20.
Inducible and conditional transgenic mouse models of schizophrenia.
Pletnikov MV.
Source
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected]
Abstract
Schizophrenia is a devastating disorder. Despite the advance in research techniques in the last couple of decades, the pathogenesis of the disorder still remains poorly understood. Given the lack of pathognomonic feature of the disease and difficulty to analyze molecular pathways in patients, animal models have been instrumental in advancing our understanding of the disease. Recent progress in genetics has identified candidate susceptibility genes for schizophrenia, and generation of new genetic animal models has begun to provide valuable insights into the disease development. However, the complex neurodevelopmental and heterogeneous nature of schizophrenia still poses tremendous challenges for creating credible mouse models. In this review, we will discuss how current genetic systems of temporal and conditional regulation of gene expression have shed lights on the functions of the candidate genes in mouse models of schizophrenia. We also consider the strength and weaknesses of each model. We will argue that further development of more sophisticated genetic animal models is crucial for clarifying the unknowns of schizophrenia.
2009 Elsevier B.V. All rights reserved.
PMID: 20302816 [PubMed - indexed for MEDLINE]
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10.
Curr Protoc Neurosci. 2007 Apr;Chapter 9:Unit 9.24. doi: 10.1002/0471142301.ns0924s39.
Overview of animal models of schizophrenia.
Powell SB, Geyer MA.
Source
University of California, San Diego, La Jolla, California, USA.
Abstract
Animal models of schizophrenia may increase the understanding of the neurological abnormalities associated with the disorder and aid in the development of rational pharmacological treatments. Rather than attempting to model the entire syndrome of schizophrenia, a more biologically oriented approach to animal models has been to focus on specific symptoms of schizophrenia that are more objectively measured in the clinical population and more directly translatable to animals (e.g., observables or endophenotypes). This overview focuses on behavioral measures that have been investigated in rodent models of schizophrenia with varying degrees of predictive, etiological, and construct validity. Because of the severity of cognitive deficits in schizophrenia and their resistance to current treatments, there is a need to develop animal models specific to the cognitive symptoms of schizophrenia. In light of this need, this overview discusses rodent models of cognition with relevance to the core cognitive deficits observed in schizophrenia.
PMID: 18428667 [PubMed - indexed for MEDLINE]
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11.
Psychopharmacology (Berl). 2006 Nov;189(1):95-104. Epub 2006 Sep 15.
Assessment of cognitive function in the heterozygous reeler mouse.
Krueger DD, Howell JL, Hebert BF, Olausson P, Taylor JR, Nairn AC.
Source
Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, Ribicoff Research Facilities, CMHC, 34 Park Street, New Haven, CT 06508, USA.
Abstract
RATIONALE:
The heterozygous reeler mouse has been proposed as a genetic mouse model of schizophrenia based on several neuroanatomical and behavioral similarities between these mice and patients with schizophrenia. However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal-cortex-dependent cognitive function, has yet to be determined.
OBJECTIVE:
Here, we investigated multiple aspects of cognitive function in heterozygous reeler mice that are known to be impaired in schizophrenic patients.
METHODS:
Heterozygous reeler mice were assessed for (1) cognitive flexibility in an instrumental reversal learning task, (2) impulsivity in an inhibitory control task, (3) attentional function in a three-choice serial reaction time task, and (4) working memory in a delayed matching-to-position task.
RESULTS:
No differences were found between heterozygous reeler mice and wild-type littermate controls in any prefrontal-related cognitive measures. However, heterozygous reeler mice showed deficits in the acquisition of two operant tasks, consistent with a role for reelin in certain forms of learning.
CONCLUSIONS:
These findings suggest that heterozygous reeler mice may not be an appropriate model for the core prefrontal-dependent cognitive deficits observed in schizophrenia, but may model more general learning deficits that are associated with many psychiatric disorders.
PMID: 16977475 [PubMed - indexed for MEDLINE] PMCID: PMC1618791 Free PMC Article
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12.
Behav Genet. 2001 May;31(3):317-24.
Behavioral abnormalities of Zic1 and Zic2 mutant mice: implications as models for human neurological disorders.
Ogura H, Aruga J, Mikoshiba K.
Source
Tsukuba Research Laboratories, Eisai Co. Ltd., Tsukuba-shi, Ibaraki, Japan.
Abstract
Zic1 and Zic2 encode closely related zinc finger proteins expressed in dorsal neural tube and its derivatives. In previous studies, we showed that the homozygous Zic1 null mutation (Zic1-/-) results in cerebellar malformation with severe ataxia and that holoprosencephaly and spina bifida occur in homozygotes for Zic2 knockdown mutation (Zic2kd/kd). Since human ZIC2 haploinsufficiency is a cause of holoprosencephaly, the Zic2kd/kd mice are regarded as an animal model for holoprosencephaly in humans. In this study, the behavioral characteristics of the Zic1 and Zic2 mutant mice were investigated in heterozygotes (Zic1-/+ or Zic2kd/+), and significant abnormalities were found in the hanging, spontaneous locomotor activity, stationary rod (Zic1-/+), acoustic startle response, and prepulse inhibition tests (Zic2kd/+). The abnormalities in the Zic1-/+ mice may be explained in part by the hypotonia caused by hypoplasia of the cerebellar anterior vermis, and these mice are regarded as a model of Joubert syndrome. In contrast, the sensorimotor gating abnormality in the Zic2kd/+ mice may be attributable to the presumed abnormality in the dorsomedial forebrain, which was strongly affected in the Zic2kd/kd mice. Zic2kd/+ mice can serve as a model for diseases involving sensorimotor gating abnormalities, such as schizophrenia.
PMID: 11699604 [PubMed - indexed for MEDLINE]
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13.
Biol Psychiatry. 1980 Dec;15(6):909-16.
Acute and chronic LSD effects on rat startle: data supporting an LSD--rat model of schizophrenia.
Braff DL, Geyer MA.
Abstract
Animal models of human schizophrenia using LSD and related hallucinogens have been challenged on several grounds. One compelling argument against the LSD model is that while schizophrenia can be chronically debilitating, animal and human effects of LSD exhibit behavioral tolerance following chronic administration. The present study tested the effects of acute and chronic LSD on measures of rat startle, a widely used behavioral measure of reactivity and habituation. The results suggest that behavioral tolerance after chronic LSD administration is incomplete, with tolerance exhibited to the acute impairment of habituation but potentiation of startle magnitude on both the first response and the first block of 30 trials. These results are interpreted as supporting the viability of LSD as a model for one or more of the group of schizophrenias.
PMID: 7193055 [PubMed - indexed for MEDLINE]
Also, give it a try to the LAMHDI database (Link Animal Models to Human DIsease,) this is a search for schizophrenia and mouse: http://www.lamhdi.org
Hi Alok,
It also depends on what your main objective is. If you are seeking to screen new antipsychotic drugs, then you might consider models that offer predictive validity for antipsychotic effectiveness, rather than seeking one of the many putative disease models. For example, you might consider the approach use in many of Torgny Svensson's papers, which involves assessing drugs in the conditioned avoidance response (CAR) task (which is predictive of positive symptom efficacy), an inclined grid assessment or paw test (which indexes catalepsy and is predictive of extrapyramidal side effects), and microdialysis with analysis for dopamine in the medial prefrontal cortex and nucleus accumbens (all studies conducted in rats). A typical antipsychotic drug would inhibit CAR at doses that produce catalepsy and then cause a greater percent increase in dopamine concentrations in the nucleus accumbens compared to the prefrontal cortex. An atypical antipsychotic drug would inhibit CAR, but would do so at doses that do not produce catalepsy. Also, atypical antipsychotic drugs tend to have a similar or greater percentage of increased dopamine concentrations in the prefrontal cortex compared to the nucleus accumbens. There are also many other approaches for screening antipsychotic drugs, if that is what you are planning to do.
Hi Alok and Adam:
Totally agree with Adam if you are looking for antipsychotic drug screening tests, and they are known for strong predictive validity.
If on the other hand you are looking for true animal models of schizophrenia, things get somewhat more tricky. Did recently read an interesting review on the topic by Desbonnet, O'Tuathaigh and Waddington 'Modeling Schizophrenia', Expert Rev Clin Pharmacol 5:667676, 2012, though. You may want to check that one out.
Good luck, Marie-Louise Wadenberg (www.wamalabs.com)
It is probably a much better strategy to study symptoms rather than diseases, especially as it does not make much sense to speak about schizophrenic rats. One such is auditory hallucinations, and there are perfectly good animal models for tinnitus which can be used, since, as Kraepelin described, tinnitus and hallucinations fall upon a continuous distribution and cannot be defined apart.
Some simple models I would like to suggest for Schizophrenia:
1. Pole climb avoidance in rats (Cook's pole climbing apparatus)
2. Brain self stimulation in rats
3. Influence on behavior of cotton rat (Sigmodon hispidus)
To Refer these models, you can read Vogel GR - Book for models, used for evaluation of drug activity...
There are some fantastic suggestions by everyone in this chain of answers. Great ideas for work being done to improve on animal models.
I just wanted to add the importance of the "default mode" in mental disorders including schizophrenia. See : Default-mode brain dysfunction in mental disorders: a systematic review. by Broyd et al 2009. and Failure to deactivate in the the prefrontal cortex in schizophrenia: dysfunction of the default mode network? Pomarol-Clotet et al 2008. We need to find a bridge for this brain region's function in rodents, we do not have this worked out yet. Is it a social cognitive link ? I think this would greatly add to the value of rodents as animal models for schizophrenia.
"I just wanted to add the importance of the "default mode" in mental disorders including schizophrenia"
But we have no idea wheher the DM is a cause or result of the symptoms of schizophrenia, so animal models of this would be uninterpretable (unlike an animal model for hallucinations as previously mentioned above).
It appears it could be an important a risk factor (default mode) and its impairment correlates well with severity of symptoms in patients. Its an interesting approach and is looking at susceptible genes.
Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia
Susan Whitfield-Gabrielia1 et al. 2008 PNAS Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.
We have been looking at symptoms for a long time and that is all we have are drugs that work on symptoms. We have not been able to prevent the development of schizophrenia.
"It appears it could be an important a risk factor (default mode) and its impairment correlates well with severity of symptoms in patients."
Which is perfectly consistent with the idea that DM anomalies are secondary to the symptoms.
"We have been looking at symptoms for a long time and that is all we have are drugs that work on symptoms."
So it makes more sense, and is much more straightforward, to model symptoms of disease, like hallucinations, rather than trying to create a schizophrenic mouse.
"In this study we used two rat models of schizophrenia-like behavior"
The test for schizophrenia was PPI of the acoustic startle reflex, which is also used to test for incipient deafness in rodents. So what was the state of the cochlea in these animals? On Mar 11, 2013, in answer to this RG question, I suggested an animal model of tinnitus was a suitable model for auditory hallucinations in psychosis or otherwise.
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