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.

Keywords: animal models; laboratory rodents; model validity; neurobiology; schizophrenia; schizophrenia symptoms; zebrafish.

Figure 1

Comparison of zebrafish, rat and human brain morphologies. (A) Differences in mammalian and zebrafish CNS ontology. (B, C) Scheme of human, rat and zebrafish homological brain areas mostly alternated in schizophrenia. Figures were modified from –, .