Advantages and Limitations of Animal Schizophrenia Models

Białoń, Magdalena; Wąsik, Agnieszka

doi:10.3390/ijms23115968

Cited by 55 publications

(36 citation statements)

References 275 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In fact, animal models cannot fully mirror the complexity of human behaviors and only indirectly reflect psychotic phenotypes, especially for cognitive dysfunction and negative symptoms of schizophrenia [ 167 ]. The pharmacological treatments modeling psychotic-like behaviors could affect different neurotransmitter pathways and represent a further source for heterogeneity in terms of antipsychotics-induced IEGs expression, brain connectivity, and effectiveness in counteracting behavioral abnormalities [ 168 ]. In this regard, most studies included in the present review evaluated changes in fMRI and electrophysiological parameters exerted by antipsychotics in murine models of psychosis, especially but not exclusively set by the administration of NMDAR antagonists.…”

Section: Discussionmentioning

confidence: 99%

Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance

Bartolomeis¹,

Simone²,

Ciccarelli³

et al. 2022

Biomedicines

View full text Add to dashboard Cite

Schizophrenia is a severe mental illness characterized by alterations in processes that regulate both synaptic plasticity and functional connectivity between brain regions. Antipsychotics are the cornerstone of schizophrenia pharmacological treatment and, beyond occupying dopamine D2 receptors, can affect multiple molecular targets, pre- and postsynaptic sites, as well as intracellular effectors. Multiple lines of evidence point to the involvement of antipsychotics in sculpting synaptic architecture and remodeling the neuronal functional unit. Furthermore, there is an increasing awareness that antipsychotics with different receptor profiles could yield different interregional patterns of co-activation. In the present systematic review, we explored the fundamental changes that occur under antipsychotics’ administration, the molecular underpinning, and the consequences in both acute and chronic paradigms. In addition, we investigated the relationship between synaptic plasticity and functional connectivity and systematized evidence on different topographical patterns of activation induced by typical and atypical antipsychotics.

show abstract

Section: Discussionmentioning

confidence: 99%

Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance

Bartolomeis¹,

Simone²,

Ciccarelli³

et al. 2022

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Animal models of psychiatric disorders have many limitations and cannot fully reflect the conditions observed in humans ( Białoń and Wa̧sik, 2022 ). The NVHL model is inadequate for assessing the functionality of protein changes observed in schizophrenia patients, and future studies are needed to determine whether similar results can be obtained in transgenic animals.…”

Section: Discussionmentioning

confidence: 99%

Alterations in prefrontal cortical neuregulin-1 levels in post-pubertal rats with neonatal ventral hippocampal lesions

Watanabe

Nakagawasai²,

Kanno³

et al. 2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Genetic studies in humans have implicated the gene encoding neuregulin-1 (NRG-1) as a candidate susceptibility gene for schizophrenia. Furthermore, it has been suggested that NRG-1 is involved in regulating the expression and function of the N-methyl-D-aspartate receptor and the GABAA receptor in several brain areas, including the prefrontal cortex (PFC), the hippocampus, and the cerebellum. Neonatal ventral hippocampal lesioned (NVHL) rats have been considered as a putative model for schizophrenia with characteristic post-pubertal alteration in response to stress and neuroleptics. In this study, we examined NRG-1, erb-b2 receptor tyrosine kinase 4 (erbB4), and phospho-erbB4 (p-erbB4) levels in the PFC and the distribution of NRG-1 in the NVHL rats by using immunoblotting and immunohistochemical analyses. Neonatal lesions were induced by bilateral injection of ibotenic acid in the ventral hippocampus of postnatal day 7 Sprague-Dawley (SD)-rats. NVHL rats showed significantly decreased levels of NRG-1 and p-erbB4 in the PFC compared to sham controls at post-pubertal period, while the level of erbB4 did not differ between sham and NVHL rats. Moreover, microinjection of NRG-1 into the mPFC improved NVHL-induced prepulse inhibition deficits. Our study suggests PFC NRG-1 alteration as a potential mechanism in schizophrenia-like behaviors in the NVHL model.

show abstract

“…Other pharmacological intervention paradigms involves acute ketamine (20 mg/kg intraperitoneal (i.p)) administered in rats inducing decreased memory performance; subchronic ketamine (20 mg/kg, i.p) administered in mice for 7 or 14 days inducing hyperlocomotor activity, decreased sociability and decreased spatial and recognition memory performance; subchronic ketamine (25 mg/kg i.p) administered in rats for 7 days inducing hyperlocomotor activity, decreased no. of social contacts and PPI deficits; and subchronic ketamine (20 mg/kg i.p) administered in mice for 14 days inducing PPI deficits, decreased memory performance and social preference [ 43 ].…”

Section: Animal Models Of Schizophreniamentioning

confidence: 99%

“…or subchronic PCP (10 mg/kg subcutaneous (s.c)) for 10 days administered in mice inducing hyperlocomotor activity, increased immobility time in FST and decreased memory performance while as subchronic PCP (2 mg/kg i.p. 2 × day) administered in rats for 7 days inducing decreased performance in attentional set-shifting tasks [ 43 ].…”

Section: Animal Models Of Schizophreniamentioning

confidence: 99%

“…The pharmacological intervention paradigms involve acute MK-801 (0.1 mg/kg i.p.) administered in rats inducing decreased spatial and recognition memory performance; subchronic MK-801 (0.1 mg/kg i.p) for 7 days administered in mice inducing decreased locomotor activity, decreased sociability and PPI deficits; and subchronic MK-801 (1 mg/kg i.p) administered in mice for 14 days inducing hyperlocomotor activity, decreased sociability and PPI deficits [ 43 ].…”

Section: Animal Models Of Schizophreniamentioning

confidence: 99%

See 1 more Smart Citation

Understanding translational research in schizophrenia: A novel insight into animal models

et al. 2023

View full text Add to dashboard Cite

Schizophrenia affects millions of people worldwide and is a major challenge for the scientific community. Like most psychotic diseases, it is also considered a complicated mental disorder caused by an imbalance in neurotransmitters. Due to the complexity of neuropathology, it is always a complicated disorder. The lack of proper understanding of the pathophysiology makes the disorder unmanageable in clinical settings. However, due to recent advances in animal models, we hope we can have better therapeutic approaches with more success in clinical settings. Dopamine, glutamate, GABA, and serotonin are the neurotransmitters involved in the pathophysiology of schizophrenia. Various animal models have been put forward based on these neurotransmitters, including pharmacological, neurodevelopmental, and genetic models. Polymorphism of genes such as dysbindin, DICS1, and NRG1 has also been reported in schizophrenia. Hypothesis based on dopamine, glutamate, and serotonin are considered successful models of schizophrenia on which drug therapies have been designed to date. New targets like the orexin system, muscarinic and nicotinic receptors, and cannabinoid receptors have been approached to alleviate the negative and cognitive symptoms. The non-pharmacological models like the post-weaning social isolation model (maternal deprivation), the isolation rearing model etc. have been also developed to mimic the symptoms of schizophrenia and to create and test new approaches of drug therapy which is a breakthrough at present in psychiatric disorders. Different behavioral tests have been evaluated in these specific models. This review will highlight the currently available animal models and behavioral tests in psychic disorders concerning schizophrenia.

show abstract

Advantages and Limitations of Animal Schizophrenia Models

Cited by 55 publications

References 275 publications

Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance

Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance

Alterations in prefrontal cortical neuregulin-1 levels in post-pubertal rats with neonatal ventral hippocampal lesions

Understanding translational research in schizophrenia: A novel insight into animal models

Contact Info

Product

Resources

About