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Neurobehavioral consequences of experimental psychosis in laboratory rats
Svojanovská, Markéta ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Schizophrenia is a serious neuropsychiatric disease with a lifetime prevalence of 1% and it disrupts almost all mental functions. It manifests with many symptoms, which can be roughly classified into three main classes - positive, negative and cognitive dysfunctions. The psychosis, which can be often seen in schizophrenia, is a very serious problem that along with all other symptoms influences the patients' clinical status as well as quality of their life. As no direct causes or causal treatments for schizophrenia are known, scientist often focus on animal models of schizophrenia as tools for investigating mechanisms that can take a part in real disease and for seeking novel antipsychotics. This thesis aims at investigating two-week subchronic treatment with dizocilpine (MK-801), a non-competitive antagonist of NMDA receptors, in Wistar and Long-Evans rats aged 30 (PND 30) and 60 days (PND 60) at the onset of the treatment. Subsequently, long-term neurobehavioral consequences of this experimental psychosis were studied by testing rats at three behavioral tasks: the Elevated-plus maze (EPM), the Morris water maze (MWM) and active place avoidance on a rotating arena (Carousel). The Western blot method was used to determine post-mortem changes in expression of the NR1, NR2A and NR2B subunits of the...
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Animal models of schizophrenia based on NMDA receptors
Svojanovská, Markéta ; Stuchlík, Aleš (advisor) ; Bendová, Zdeňka (referee)
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system responsible for information processing including learning and memory. Its concentration must be maintained at the correct physiological levels because a deficiency or an excess of glutamate can cause variety of disruptions of CNS function. Glutamate acts also via the NMDA receptor, a specific type of ionotropic glutamate receptor. A number of studies have suggested that glutamatergic NMDA receptors play an important role in an ability to learn, memory, brain development and brain function. Importantly, their reduced function is considered as a possible factor for the pathogenesis of schizophrenia. The NMDA receptor hypofunction hypothesis settles on findings that non-competitive NMDA receptor antagonists such as ketamine, phencyclidine and dizocilpine (MK-801) can induce schizophrenic-like symptoms in healthy individuals and exacerbates symptoms in schizophrenic patients; therefore they are often used in animals to induce schizophrenia-like behavior. All these animal models contribute to a better understanding of the etiology and pathophysiology of schizophrenia and may serve as a useful tool in searching for new antipsychotic agents. Key words: glutamate, schizophrenia, memory, NMDA receptors,...
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