Animal models of schizophrenia

Jones, Caitlin A.; Watson, David J.; Fone, Kevin C. F.

doi:10.1111/j.1476-5381.2011.01386.x

Cited by 665 publications

(575 citation statements)

References 379 publications

(564 reference statements)

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“…The researchers paralleled these findings to negative symptoms observed in schizophrenia. It is important to note that the negative symptoms of schizophrenia have received less attention than positive symptoms within research that employs animal models to better understand this disorder (Jones, Watson, & Fone, 2011).…”

Section: Introductionmentioning

confidence: 99%

6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure.

Elcoro¹,

Thompson²,

Kelly³

et al. 2014

Psychology & Neuroscience

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Impaired temporal control is symptomatic of several neurological disorders; recently, it has been implicated in schizophrenia. An animal model of schizophrenia using 6-hydroxydopamine (6-OHDA) infused to the medial pre-frontal cortex (mPFC) was employed to examine its effects on temporal control. Twelve rats were trained on a peak-interval procedure (PIP) until stable patterns of behavior were obtained. Rats infused with 6-OHDA responded less during peak trials and their peak functions were flatter than sham rats. These results are consistent with similar studies with transgenic mice with increased striatal dopamine D2 receptor activity. Lesions in the mPFC decreased motivation to respond in a PIP. These effects may be considered analogous to negative symptoms of schizophrenia.

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Section: Introductionmentioning

confidence: 99%

6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure.

Elcoro¹,

Thompson²,

Kelly³

et al. 2014

Psychology & Neuroscience

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“…Anatomically, DISC1 knockin mice show increased lateral ventricle size, reduced cortical and hippocampal size like those found in schizophrenic patients [51] . Also, the expression of several proteins changes in the brain of schizophrenic patients such as "dysbindin" encoded by the gene DTNBP1, which is thought to be one of the most promising candidate genes for schizophrenia [52] .…”

Section: Possible Genetic Monkey Models Of Schizophrenia In the Near mentioning

confidence: 82%

Section: Possible Genetic Monkey Models Of Schizophrenia In the Near mentioning

confidence: 98%

“…Partial knockout of NRG1 in mice causes social interaction problems, reduced prepulse inhibition, and higher levels of spontaneous locomotion. These symptoms are reduced by clozapine [51] .It used to be quite diffi cult to perform genetic manipulation in monkeys, but at present, these techniques are rapidly developing in nonhuman primates [53,54] . Thus it will be possible to develop genetic monkey models for schizophrenia by genetic manipulation techniques in the near future.…”

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confidence: 99%

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Prefrontal dysfunction and a monkey model of schizophrenia

et al. 2015

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The prefrontal cortex is implicated in cognitive functioning and schizophrenia. Prefrontal dysfunction is closely associated with the symptoms of schizophrenia. In addition to the features typical of schizophrenia, patients also present with aspects of cognitive disorders. Based on these relationships, a monkey model mimicking the cognitive symptoms of schizophrenia has been made using treatment with the non-specific competitive N-methyl-D-aspartate receptor antagonist, phencyclidine. The symptoms are ameliorated by atypical antipsychotic drugs such as clozapine. The benefi cial effects of clozapine on behavioral impairment might be a specifi c indicator of schizophrenia-related cognitive impairment. Keywords: prefrontal cortex; schizophrenia; monkey model ·Review· IntroductionOne percent of the adult population, particularly young adults, are affected by schizophrenia. Schizophrenic patients typically present with hallucinations, delusions, withdrawal from social activities, loss of personal care skills, and flat or inappropriate emotional responses to situations [1] . Although many factors have been associated with schizophrenia, including genetic factors, early environmental influences, and neurobiological, psychological, and sociological processes [2][3][4] that are very important contributory factors, the mechanism underlying this disorder is unknown. Patient data are insufficient for understanding the pathology and etiology of schizophrenia.Further, direct experimentation on human subjects is ethically unacceptable. Thus, animal models have become an indispensable tool for pathological research. Unlike other neurological diseases such as stroke, epilepsy, and Parkinson's disease that can be easily replicated in animals, some of the symptoms of schizophrenia human patients, such as thinking disorders, delusions, and hallucinations, are difficult to replicate in animals.For many years, there has been no appropriate nonhuman primate model of schizophrenia. In addition to the typical features of schizophrenia, patients present with aspects of prefrontal cognitive disorders involving, e.g., working memory, selective attention, initiating movement, and planning. Based on these relationships, a monkey model of schizophrenia could be developed by mimicking its cognitive symptoms. In this review, we introduce schizophrenia and the prefrontal cortex (PFC) as well as their relationship and discuss the development of a monkey model of schizophrenia, including the methods and behavioral tests of the model. The Prefrontal Cortex and SchizophreniaThe volume of the human brain is twice that of the chimpanzee, and the PFC, which is the most rostral component of the primate cortex, has expanded most in humans [5,6] . In other species, the PFC functions in voluntary motor control, whereas in primates, it has developed [5][6][7] . The PFC has broad connections with many parts of the brain, particularly the sub-regions of the limbic system [10] . The human PFC, which is better developed than in other primates, is the primary ...

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“…PCP is a psychotomimetic (positive symptoms) agent, 1, 2 which is also able to induce negative 1,3 and cognitive [4][5][6][7][8] symptoms of schizophrenia and other psychiatric disorders, in humans and rodents. 9,10 In addition, it can exacerbate these symptoms in schizophrenia patients. 11 Thus, studies of PCP feature prominently in pharmaceutical drug discovery efforts since most current treatments of schizophrenia are predominately tailored against the positive symptoms, while negative and cognitive symptoms tend to be resistant to current antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal Proteomic and Metabonomic Abnormalities in Neurotransmission, Oxidative Stress, and Apoptotic Pathways in a Chronic Phencyclidine Rat Model

et al. 2015

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Schizophrenia is a neuropsychiatric disorder affecting 1% of the world's population. Due to a broad range of symptoms and wide heterogeneity, current therapeutic approaches in schizophrenia fail to treat all symptomatic manifestations of the disease. Therefore, new models that reproduce core pathological features of schizophrenia are needed for the elucidation of unidentified pathological disease mechanisms. Here, we employ a comprehensive global label-free liquid chromatographymass spectrometry (LC-MS) proteomic and metabonomic profiling analysis combined with targeted proteomics (selected reaction monitoring and multiplex-immunoassay) of serum and brain tissues from a chronic phencyclidine (PCP) rat model, in which NMDA-receptor hypofunction is induced through non-competitive N-methyl-D-aspartate (NMDA) antagonism. Using multiplex immunoassay, we identified serum abnormalities in cytokines (IL-5, IL-2, IL-1β) and the fibroblast-growth factor-2 levels, as peripheral biomarkers of PCP treatment. In order to find potential novel drug targets and to elucidate the pathways associated with the disease, extensive proteomic and metabonomic brain tissue profiling was employed. This revealed a more prominent effect of chronic PCP treatment on the hippocampal proteome and metabonome compared to the frontal cortex. Bioinformatic pathway analysis confirmed the abnormalities in NMDA-receptor associated pathways in both brain regions, as well as alterations in other neurotransmitter systems such as kainate, AMPA and GABAergic signalling in the hippocampus. Metabonomic profiling revealed changes in phospho-and glycolipids, which was further supported by findings of oxidative stress (superoxide dismutase) on the protein level. These molecular changes parallel findings observed in human schizophrenia. The present study could lead to increased understanding of how perturbed glutamate receptor signalling affects other relevant biological pathways in schizophrenia and therefore support drug discovery efforts for improved treatment of patients suffering from this debilitating psychiatric disorder.

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Animal models of schizophrenia

Cited by 665 publications

References 379 publications

6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure.

6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure.

Prefrontal dysfunction and a monkey model of schizophrenia

Hippocampal Proteomic and Metabonomic Abnormalities in Neurotransmission, Oxidative Stress, and Apoptotic Pathways in a Chronic Phencyclidine Rat Model

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