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    Avaliação do papel da D-serina na modulação da resposta de inibição por pré-pulso do reflexo de sobressalto acústico em um modelo animal de esquizofrenia: ratos wistar machos tratados agudamente com MK-801
    (Universidade Federal de São Paulo (UNIFESP), 2021) Santos, Nara Henriques [UNIFESP]; Silva, Regina Cláudia Barbosa da [UNIFESP]; Universidade Federal de São Paulo
    Schizophrenia is a mental disorder that affects approximately 1% of the world population, being a chronic and debilitating pathology. One of the neurochemical hypotheses related to schizophrenia is the existence of a dysfunction in the glutamatergic system characterized by a hypofunction of N-methyl-D-Aspartate (NMDA) receptors. MK-801 is a non-competitive glutamatergic antagonist that works by blocking NMDA receptors activity. Rats systemically treated with MK-801 show behavioral changes traditionally associated with animal models of schizophrenia. The aim of this study is to evaluate the effects of acute administration of dizocilpine (MK-801), an NMDA antagonist, on the Pre-Pulse Inhibition (IPP) responses of the acoustic startle reflex and the startle amplitude in rats. The IPP response correlates with the cognitive symptoms of schizophrenia. Furthermore, it was investigated whether pretreatment with D-Serine (glutamatergic co-agonist) could prevent possible PPI deficits induced by acute administration of MK-801. Forty male Wistar rats weighing 300-350g from the Center for the Development of Experimental Models for Medicine and Biology (CEDEME) were used. The following drugs were used: Dizocilpine (MK-801) and D-Serine both were diluted in physiological saline, which was also used as a control vehicle. Experimental groups: Saline + Saline; Saline + MK-801); D-Serine + Saline; D-Serine + MK-801. After a 7-day habituation period, the rats were submitted to a balancing session and, on the following day,underwent the IPP test.Data were presented as mean ± SEM. The mean PPI was submitted to two-way analysis of variance (ANOVA) with repeated measures. One-way ANOVA was used for startle amplitude response. In case of statistical significance, the Bonferroni post hoc test was applied. A P value equal to or less than 0.05 was considered significant. The results of this study showed that rats in the saline/MK-801 group had IPP deficits compared to the other groups, indicating behavioral changes in rats treated with MK-801. Pre-treatment with D-Serine, however, was not able to prevent the PPI deficits observed in the MK-801 group. We hypothesized that the dose used in this study did not alter the levels of brain concentration of D-Serine to the point of producing any behavioral effect. The startle response amplitude was not altered by the treatments, ruling out any motor impairment in the animals and showing the selective effect of MK-801 on the PPI deficit.