In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

Abstract

Schizophrenia (SZ) is a complex psychiatric disorder characterized by positive, negative, and cognitive symptoms, and is not satisfactorily treated by current antipsychotics. Progress in understanding the basic pathomechanism of the disease has been hampered by the lack of appropriate models. In order to develop modern drugs against SZ, efficient methods to study them in in vitro and in vivo models of this disease are required. In this review a short presentation of current hypotheses and concepts of SZ is followed by a description of current progress in the field of SZ experimental models. A critical discussion of advantages and limitations of in vitro models and pharmacological, genetic, and neurodevelopmental in vivo models for positive, negative, and cognitive symptoms of the disease is provided. In particular, this review concerns the important issue of how cellular and animal systems can help to meet the challenges of modeling the disease, which fully manifests only in humans, as experimental studies of SZ in humans are limited. Next, it is emphasized that novel clinical candidates should be evaluated in animal models for treatment-resistant SZ. In conclusion, the plurality of available in vitro and in vivo models is a consequence of the complex nature of SZ, and there are extensive possibilities for their integration. Future development of more efficient antipsychotics reflecting the pleiotropy of symptoms in SZ requires the incorporation of various models into one uniting model of the multifactorial disorder and use of this model for the evaluation of new drugs.

Application of animal experimental models in the research of schizophrenia

“…It plays a key role in neuronal synapse formation, neuron migration and synaptic plasticity. Numerous biological studies have confirmed the role of DISC1 in early neurodevelopment and synaptic regulation (Brandon & Sawa, 2011; Koszla, Targowska‐Duda, Kedzierska, & Kaczor, 2020; Lee et al, 2011; Millar et al, 2000; Soares, Carlyle, Bradshaw, & Porteous, 2011; St Clair et al, 1990). Following the discovery of this gene, researches using model organisms to examine the biological functions of DISC1 have achieved fruitful results.…”

The Importance of Studying Human Brain

“…It is not only that normal structure of the human brain is a fascinating topic for research, but the diseased brain is even more exciting. It has been self-evident that complex psychiatric disorders such as depression, schizophrenia, autism are human-specific and, although attempts of animal models exist, they are limited to model only certain aspects of disease (43,44,45). Furthermore, many neurological disorders, such as multiple sclerosis, Huntington's, Parkinson's and Alzheimer's disease, have not been reported to occur spontaneously in the animal kingdom, and even their animal models fail to reproduce the main symptoms and progression of disease (46,47,48,49).…”

The dilemma of polypharmacy in psychosis: is it worth combining partial and full dopamine modulation?

“…ligand binding assay) to assess their receptor binding affinity. This step is essential to predict in-vivo efficacy of drug candidates ( Hughes et al , 2011 ; Koszła et al , 2020 ). Indeed, in-vivo efficacy is closely related to receptor site occupancy.…”