The Role of Zebrafish and Laboratory Rodents in Schizophrenia Research

Abstract

Schizophrenia is a severe disorder characterized by positive, negative and cognitive symptoms, which are still not fully understood. The development of efficient antipsychotics requires animal models of a strong validity, therefore the aims of the article were to summarize the construct, face and predictive validity of schizophrenia models based on rodents and zebrafish, to compare the advantages and disadvantages of these models, and to propose future directions in schizophrenia modeling and indicate when it is reasonable to combine these models. The advantages of rodent models stem primarily from the high homology between rodent and human physiology, neurochemistry, brain morphology and circuitry. The advantages of zebrafish models stem in the high fecundity, fast development and transparency of the embryo. Disadvantages of both models originate in behavioral repertoires not allowing specific symptoms to be modeled, even when the models are combined. Especially modeling the verbal component of certain positive, negative and cognitive symptoms is currently impossible.

A critical review of zebrafish schizophrenia models: Time for validation?

“…In addition to other functions, the influx of calcium into the cell regulates neuronal gene expression and neurotransmitter release (West, Griffith and Greenberg, 2002;Devor et al, 2017). Moreover, another hypothesis regarding the pathophysiology of PDs such as SCZ relates to imbalances in the levels of various neurotransmitters (Patel et al, 2014;Sigitova et al, 2017;Langova et al, 2020).…”

“…tonic-clonic seizures manifest as hyperlocomotor activity while absence seizures may manifest as hypolocomotor activity. In addition, hyperlocomotion is sometimes used an endophenotype of psychosis in animal models (Seibt et al, , 2011de Bartolomeis et al, 2013;Langova et al, 2020). Although the sa15296 mutants were hypoactive, the LFP traces suggested they had seizure-like activity.…”

“…Psychotropic drugs that either increase the release or decrease the reuptake of dopamine leads to psychotic and manic symptoms (Ecker et al, 2009). On the other hand, antipsychotics and other dopamine antagonists decrease psychotic or manic episodes (Patel et al, 2014;Langova et al, 2020). Similarly, dysregulation in excitatory neurotransmission is associated with psychiatric endophenotypes of SCZ, BP, and depression (de Patel et al, 2014;Sigitova et al, 2017).…”

“…NMDA-R antagonists such as MK-801, phenycycline and ketamine have been shown to induce psychotic like symptoms in animal models and together with dopamine agonists (e.g. apomorphine, amphetamine) are commonly used as pharmacological models of SCZ (de Langova et al, 2020).…”

Zebrafish: A Promising Real-Time Model System for Nanotechnology-Mediated Neurospecific Drug Delivery

“…However, the use of zebrafish as a model system has its limitations too. First and foremost, the nervous system of the zebrafish may not be as complicated and developed as that in humans; the rodent and murine nervous systems are comparatively better developed and can be used to study the complex human brain diseases; however, they are not identical to that of humans [ 22 ]. Secondly, the zebrafish lacks some organ systems found in humans like the lungs, prostate and the mammary glands; also, diseases caused by genes absent in the zebrafish cannot be studied [ 23 ].…”