Browsing by Subject "NMDAR antagonists"

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  • Törnävä, Marja (Helsingfors universitet, 2012)
    Literature review: Cognitive deficits of schizophrenia include disturbances in executive functions, working memory, attention and information processing. Improved understanding of the neurobiology of these deficits depends on the availability of reliable and carefully validated animal models, which can assist the development of novel pharmacotherapies. The glutamate hypothesis of schizophrenia arises from observations that substances which block a type of glutamate receptor known as N-methyl-D-aspartate-receptor (NMDAR) induces schizophrenia-like condition. The evidence strongly supports the use of NMDAR antagonists to model schizophrenia in animals. In this literature review various cognitive animal models of schizophrenia are presented. Also heterogeneity in the effects of NMDAR antagonists, at the cognitive level, following single-dose or long-term exposure is reviewed and discussed. Experimental part: Attentional set shifting task (ASST) is a cognitive animal model, which models animal's cognitive flexibility or ability to shift attentional set. The ASST has been modified for use with mice. Validation of the test in mice is still inadequate. The main purpose of this study was to investigate whether ASST is suitable for an outbred ICR mouse strain. The current study failed to demonstrate the suitability of ICR mice in this test. Though results did prove that ICR mice are capable of performing the technical requirements of the test. The pharmacological focus of this study was to investigate in mice how a subchronically administrated NMDAR antagonist dizocilpine (MK-801) (0.03-0.1 mg/kg, 10-14 d, i.p.) influences the ability to shift attentional set. With our experimental design we could not measure the ability to shift attentional set thus we cannot conclude whether or not MK-801 influenced this cognitive domain. Results did reveal that MK-801, as administrated above, did not alter the motivation or motor functions in ICR mice. According to literature and this current study it is obvious that more research is needed to clear ASST suitability for mice. Future studies should focus to investigate how the components of the experimental arrangement in ASST affect the test performance.