The experimental models of schizophrenia are based on morphological, biochemical and genetic findings in the clinical population. These models serve as an important tool for the research of etiology and pathophysiology, and for testing novel potential treatment methods. The experimental models of schizophrenia are divided into neurodevelopmental, pharmacological and genetic. Only the pharmacological model is useful in humans.

An important role of the glutamatergic neurotransmitter system in the pathogenesis of schizophrenia has been supported by findings on various levels from molecular interactions up to the structural layout of the neuronal network in the human brain. The research of the glutamatergic system in schizophrenia has advanced with the use of non-competitive antagonists of glutamate NMDA receptors (phencyclidine, ketamine, and dizocilpine). These compounds change both human and animal behavior and induce schizophrenia-like manifestations in the field of different neurobiological modalities and markers.

The models based on both acute and chronic administration of non-competitive antagonists of glutamate NMDA receptors in humans and rats show phenomenological validity and are suitable for searching for new substances with antipsychotic effects. In particular, the human model of schizophrenia based on infusion of ketamine exerts high face validity in term of induction both positive and negative symptoms, and characteristic cognitive, electrophysiological (qEEG) and metabolic (PET) changes.

Nevertheless, the pathophysiology of schizophrenia remains unexplained. In the light of the neurodevelopmental model of schizophrenia based on the early administration of NMDA receptor antagonists, it seems that increased cellular destruction by apoptosis or changes in function of glutamatergic NMDA receptors in the early development of the central nervous system are decisive for subsequent development of psychosis, which often does not manifest itself until adulthood. Chronic administration of NMDA (not applicable in humans) antagonists initializes a number of adaptation mechanisms, which correlate with findings obtained in patients with schizophrenia; therefore, this animal model is necessary for research into the pathophysiology of this disease.

This work was supported by project 1M0517 from the MEYS Czech Republic