Behavioural and neurochemical effects of post-weaning social isolation in rodents—Relevance to developmental neuropsychiatric disorders

Fone, Kevin C. F.; Porkess, M. V.

doi:10.1016/j.neubiorev.2008.03.003

Cited by 769 publications

(662 citation statements)

References 203 publications

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“…However, the mice were able to see, hear, and smell their neighbor. Thus, a social encounter with an unfamiliar conspecific through a mesh partition is considered a form of psychological stress, and it is useful for studies of the neurochemical changes that may be involved in the abnormal behaviors of isolation-reared animals (Ago et al, 2012;Fone and Porkess, 2008;Lukkes et al, 2009a, b;Pinna et al, 2008). In this study, the total time that the resident mice spent near the partition and the total time the resident and intruder mice spent interacting did not differ between the male group-reared, female isolation-reared, and male isolation-reared mice (Figure 1c).…”

Section: Discussionmentioning

confidence: 99%

“…Being raised in social isolation from early in life causes abnormal behaviors in adulthood, such as hyperlocomotion, aggressive behavior, deficits of prepulse inhibition, cognitive impairments, decreased social contact, and depression-and anxiety-like behavior in rodents (Ago et al, 2007Fone and Porkess, 2008;Lukkes et al, 2009a, b;Zhao et al, 2009). Post-weaning social isolation is a useful model to study the effects of adverse early-life experiences on behavior and the neural mechanisms associated with isolation-induced changes in mood and anxiety (Lapiz et al, 2003;Lukkes et al, 2009c).…”

Section: Introductionmentioning

confidence: 99%

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Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Ago

Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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Isolation-reared male rodents show abnormal behaviors such as hyperlocomotion, aggressive behaviors, deficits of prepulse inhibition, and depression-and anxiety-like behaviors, but the neurochemical mechanism for the effects of psychological stress in these animals is not fully understood. This study examined the effects of social interactions between isolation-reared mice and intruder mice on brain monoaminergic systems. A cage was divided into two compartments by a mesh partition to prevent direct physical interactions. The 20-min encounter with an intruder elicited a restless and hyperexcitable state (hyperactivity) in male, but not in female, isolationreared mice, whereas encounters with a sleeping intruder or a novel object did not. Although the encounter did not affect prefrontal neuronal-activity-marker c-Fos expression, dopamine (DA) levels, or serotonin (5-HT) levels in male group-reared mice or female isolation-reared mice, it increased prefrontal c-Fos expression, DA levels, and 5-HT levels in male isolation-reared mice. Furthermore, encounter-induced increases in c-Fos expression in the dorsal raphe nucleus and ventral tegmental area, but not in the nucleus accumbens shell, were much greater in isolation-reared than group-reared male mice. A 5-HT 1A receptor agonist, a metabotropic glutamate 2/3 receptor agonist, and a gamma-aminobutyric acid A receptor agonist attenuated isolation-induced aggressive behaviors and encounter-induced hyperactivity, c-Fos expression in the prefrontal cortex and dorsal raphe nucleus, and increases in prefrontal 5-HT levels. These findings suggest that the prefrontal DA and 5-HT systems are activated by encounter stimulation in male isolationreared mice, and the encounter-induced activation of 5-HT system triggers the induction of some abnormal behaviors in male isolation-reared mice. Furthermore, this study implies that the encounter stimulation-induced signal has a pharmacological significance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Ago

Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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“…Neurodevelopmental animal models include maternal immune activation, prenatal malnutrition, the interruption of neurogenesis by methylazoxymethanol (MAM) and the neonatal ibotenic acid lesion of the ventral hippocampus 113,114 . Additional models are represented by the exposure of pregnant mice to unpredictable stress, maternal separation or birth complications [115][116][117] . All of these models have revealed behavioural deficits associated either with positive, cognitive or negative symptoms of schizophrenia, and alterations in the dopaminergic, glutamatergic, GABAergic and serotonergic systems [118][119][120][121][122][123][124] .…”

Section: Vulnerability Of Our Youth: Neurodevelopmentmentioning

confidence: 99%

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Gottschalk

Sarnyai

Guest

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Psychiatric symptoms are subjective by nature and tend to overlap between different disorders. The modelling of a neuropsychiatric disorder therefore faces challenges because of missing knowledge of the fundamental pathophysiology and a lack of accurate diagnostics. Animal models are used to test hypotheses of aetiology and to represent the human condition as close as possible to increase our understanding of the disease and to evaluate new targets for drug discovery. In this review, genetic and neurodevelopmental animal models of schizophrenia are discussed with respect to behavioural and neurophysiological findings and their association with the clinical condition. Only specific animal models of schizophrenia may ultimately lead to novel diagnostic approaches and drug discovery. We argue that molecular biomarkers are important to improve animal to human translation since behavioural readouts lack the necessary specificity and reliability to assess human psychiatric symptoms.Gottschalk MG, et al. / Rev Psiq Clín. 2013;40(1):41-50 Keywords: Translational research, neuropsychiatry, genetic, neurodevelopment, animal model, schizophrenia. ResumoSintomas psiquiátricos são subjetivos por natureza e tendem a se sobrepor entre diferentes desordens. Sendo assim, a criação de modelos de uma desordem neuropsiquiátrica encontra desafios pela falta de conhecimento dos fundamentos da fisiopatologia e diagnósticos precisos. Modelos animais são usados para testar hipóteses de etiologia e para representar a condição humana tão próximo quanto possível para aumentar nosso entendimento da doença e avaliar novos alvos para a descoberta de drogas. Nesta revisão, modelos animais genéticos e de neurodesenvolvimento de esquizofrenia são discutidos com respeito a achados comportamentais e neurofisiológicos e sua associação com a condição clínica. Somente modelos animais específicos de esquizofrenia podem, em último caso, levar a novas abordagens diagnósticas e descoberta de drogas. Argumentamos que biomarcadores moleculares são importantes para aumentar a tradução de animais a humanos, já que faltam a especificidade e a fidelidade necessárias às leituras comportamentais para avaliar sintomas psiquiátricos humanos.Gottschalk MG, et al. / Rev Psiq Clín. 2013;40(1):41-50

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“…There have been some excellent recent and extensive reviews in this subject area. These include -the use of the MATRICS test battery as a guide to using preclinical tests for studying novel targets for cognitive improvement in schizophrenia (Young et al 2009); exploration of the mechanisms by which NMDA receptor antagonism provides a relevant model of schizophrenia in animals (Jentsch and Roth, 1999;Coyle, 2006;Large, 2007-focusing on novel therapies; Morris et al 2005;Mouri et al 2007); the use of isolation rearing as a neurodevelopmental model (Fone and Porkess, 2008); and strategies for improving pharmacotherapy of schizophrenia ). In addition the debate continues concerning the value (or otherwise) of current antipsychotic medication for improvement of cognitive deficit symptoms in the clinic.…”

Section: Introductionmentioning

confidence: 99%

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

477

322

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Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro-and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive disturbances of relevance to schizophrenia in rodents and their subsequent reversal by first-and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-choice serial reaction time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel therapies for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

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Behavioural and neurochemical effects of post-weaning social isolation in rodents—Relevance to developmental neuropsychiatric disorders

Cited by 769 publications

References 203 publications

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

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