Navegando por Palavras-chave "MK-801"

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    Atypical antipsychotic olanzapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of dizocilpine (MK-801) into the inferior colliculus in rats
    (Elsevier B.V., 2013-11-15) Zangrando, Julia [UNIFESP]; Carvalheira, Renata [UNIFESP]; Labbate, Giovanna Puosso [UNIFESP]; Medeiros, Priscila [UNIFESP]; Longo, Beatriz Monteiro [UNIFESP]; Melo-Thomas, Liana [UNIFESP]; Silva, Regina Cláudia Barbosa da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviors which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. the inferior colliculus (IC) is a critical part of the auditory pathway mediating acoustic PPI. the activation of the IC by the acoustic prepulse reduces startle magnitude. Thus, the purpose of the present study was to elucidate the role of glutamatergic transmission in the IC on the expression of acoustic PPI. for that we investigated whether NMDA receptor stimulation or blockade would affect this response. Unilateral microinjections of NMDA (30 nmol/0.5 mu L) into the IC did not alter PPI while microinjections of MK-801 (30 nmol/0.5 mu L) into this structure disrupted PPI. We also examined the ability of the atypical antipsychotic olanzapine (5.0 mg/kg; i.p.) to reverse the disruption of pre-pulse inhibition produced by unilateral microinjections of MK-801 into the IC of rats. Pretreatment with olanzapine blocked MK-801-induced disruption of PPI. Altogether, these results suggest that glutamate-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic olanzapine. (C) 2013 Elsevier B.V. All rights reserved.
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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.
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    Behavioral effects of MK-801 on reserpine-treated mice
    (Elsevier B.V., 2002-04-01) Dutra, R. C.; Andreazza, A. P.; Andreatini, R.; Tufik, Sergio [UNIFESP]; Vital, Maria ABF [UNIFESP]; Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)
    The effects of dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, were studied on dopamine-related behaviors induced by reserpine treatments. This study focuses on behavioral syndromes that may used as models for Parkinson's disease, or tardive dyskinesia, and its response after glutamatergic blockage. Reserpine (1 mg/kg), administered once every other day for 4 days, produced increases in orofacial dyskinesia, tongue protrusion and vacuous chewing in mice, which are signs indicative of tardive dyskinesia. Reserpine also produced tremor and catalepsy, which are signs suggestive of Parkinson's disease. MK-801 (0.1 mg/kg), administered 30 min before the observation test, prevented the vacuous chewing movements., tongue protrusions and catalepsy induced by reserpine. However, MK-801 injection produced a significant increase of tremor in reserpine-treated mice. Reserpine (1 mg/kg), administered 90 min before the test and followed by apomophine injection (0.1 mg/kg) 5 min before the test, did not produce oral dyskinesia in mice. On the other hand, reserpine induced increases in tremor and catalepsy compared to control mice. MK-801 (0.1 mg/kg) administration attenuated the catalepsy and tremor induced by reserpine. Pretreatment with reserpine (1 mg/kg) 24 h before the observation test produced increases in vacuous chewing movements and tongue protrusion, as well as increases in tremor and catalepsy, whereas MK-801 (0.1 mg/kg) injection 90 min before the test reversed the effects of reserpine, These results show that reserpine produces different and abnormal movements, which are related to dose and schedule employed and can be considered as parkinsonian-like and tardive dsykinesia signs. the glutamatergic blockage produced by NMDA can restore these signs, such as vacuous chewing movements, tongue protrusions, catalepsy and tremor according to the employed model. (C) 2001 Elsevier Science Inc. All rights reserved.
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    Efeitos comportamentais da ovariectomia em um modelo animal neurodesenvolvimental de esquizofrenia
    (Universidade Federal de São Paulo, 2024-10-18) Souza, Jaqueline Castelani de [UNIFESP]; Abílio, Vanessa Costhek [UNIFESP]; Loss, Cassio Morais [UNIFESP]; http://lattes.cnpq.br/5880914070732996; http://lattes.cnpq.br/2393173678667897; http://lattes.cnpq.br/8323772823826849
    A esquizofrenia, um transtorno psiquiátrico do neurodesenvolvimento, tem um impacto significativo na vida dos pacientes e de seus familiares. Apesar da prevalência semelhante entre homens e mulheres, a condição apresenta características dimórficas em relação ao sexo, manifestando-se de maneira distinta em termos de idade de início, tipo e gravidade dos sintomas. Essas variações sugerem uma possível influência dos hormônios sexuais na fisiopatologia da esquizofrenia, com destaque para o estradiol. É digno de nota o aparecimento tardio e o agravamento dos sintomas em mulheres durante a peri- e pós-menopausa, um período marcado por uma queda acentuada nos níveis plasmáticos de estradiol. Diante desse cenário, o presente estudo teve como objetivo geral caracterizar o perfil comportamental de ratas adultas submetidas à ovariectomia e tratadas com um antagonista não-competitivo do receptor NMDA (MK-801) durante o período neonatal. No primeiro experimento, as fêmeas foram submetidas a tratamento diário com 0,5 mg/kg de MK-801 do DPN 05 ao DPN 12, a ovariectomia (OVX) no DPN 90 e, posteriormente, a uma série de comportamentos do DPN 120 ao DPN 140. Já no Experimento 2, as ratas receberam tratamento com 0,5 mg/kg/dia de MK-801 entre o DPN 07 e o DPN 20 e foram submetidas à cirurgia de OVX no DPN 90, passando pelas tarefas comportamentais em três momentos: entre o DPN 45-49, entre o DPN 85-89, e entre DPN 135-139. Os resultados comportamentais do Experimento 1 revelaram uma redução da atividade locomotora espontânea e induzida por psicoestimulante em animais tratados com MK-801 e OVX. Com relação ao comportamento social, foi observado alta preferência pela “zona social” em todos os grupos, especialmente nos animais OVX. O teste de PPI revelou um déficit de funcionamento do filtro sensório-motor especificamente em animais MK-801 + OVX. Por sua vez, o Experimento 2 revelou atraso da abertura vaginal de ratas tratadas com MK-801, além de aumento do perfil locomotor (DPN 136) e do número de rotações (DPN 45, 46, e 136) nos animais tratados com MK-801. Também foi observado déficit cognitivo no teste de alternação espontânea e elevada preferência social em todos os grupos do Experimento 2, mas sem qualquer prejuízo de PPI. Em resumo, os achados sugerem um possível efeito do estrógeno sobre os principais neurotransmissores associados à esquizofrenia. Essa conexão entre a regulação hormonal e os sintomas comportamentais destaca a importância da compreensão dos mecanismos neurobiológicos subjacentes à esquizofrenia, visando potenciais intervenções terapêuticas centradas nos hormônios sexuais.
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    Efeitos comportamentais do tratamento com canabidiol via aleitamento materno em um modelo neonatal de esquizofrenia
    (Universidade Federal de São Paulo, 2023-12-12) Mitu, Thais Yukari [UNIFESP]; Abílio, Vanessa Costhek [UNIFESP]; Lara, Marcus Vinicius Soares de [UNIFESP]; http://lattes.cnpq.br/6801037800131675; http://lattes.cnpq.br/2393173678667897; http://lattes.cnpq.br/5557376567544058
    A esquizofrenia é um distúrbio incapacitante do neurodesenvolvimento com prevalência mundial de cerca de 0,3%. Apesar de haver medicamentos disponíveis para o tratamento da esquizofrenia, estes promovem efeitos adversos e atuam efetivamente apenas contra os sintomas positivos. Com base nisso, alternativas terapêuticas vêm sendo estudadas, com destaque para o canabidiol (CBD), um dos principais compostos da planta Cannabis sativa. O CBD tem se mostrado uma alternativa em potencial por possuir propriedades terapêuticas tanto para os sintomas positivos quanto negativos e cognitivos da esquizofrenia, apresentar maior nível de segurança em relação a outros canabinóides, induzir menores efeitos adversos em comparação aos antipsicóticos tradicionais e não produzir efeitos psicomiméticos. Portanto, a intervenção com CBD durante períodos cruciais para o neurodesenvolvimento, como a amamentação, pode ser uma nova estratégia terapêutica preventiva para a esquizofrenia. Assim, e considerando o dimorfismo sexual relacionado aos sintomas da esquizofrenia, este projeto visa caracterizar o comportamento do modelo animal de esquizofrenia induzido por MK­801, um antagonista não competitivo dos receptores NMDA, em proles (machos e fêmeas) expostas ao CBD via amamentação. Os possíveis efeitos terapêuticos do CBD foram avaliados em dois momentos: a partir do dia pós­natal (DPN) 30 e novamente a partir do DPN90 (ainda não concluídos). Observamos diferenças sexuais tanto na resposta ao MK­801, em que os machos do modelo apresentaram um déficit de memória na tarefa de reconhecimento de objetos, quanto no tratamento com CBD, que evitou o déficit nas fêmeas do modelo MK­801 na tarefa social, aos 30 dias de idade. De grande relevância, nossos resultados apontam um efeito benéfico do CBD via aleitamento materno sobre déficits de comportamento social induzido em fêmeas jovens pelo tratamento com MK­801.
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    Interação social com um coespecífico com dor e seu possível efeito reforçador em animais controle em um modelo animal de esquizofrenia
    (Universidade Federal de São Paulo (UNIFESP), 2019-11-28) Kawamoto, Elisa Mari [UNIFESP]; Abilio, Vanessa Costhek [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The present work investigated the social interaction in mice with an animal in pain and a possible reinforcing effect induced by such interaction, as well as possible changes promoted by MK-801, an animal model of schizophrenia. We also investigated the action of antipsychotics on the changes found. Four experiments were conducted, all using adult male Swiss EPM-M2 mice. Experiment 1 (pilot study) was conducted to determine the ability of different doses of acetic acid in promoting aversion within the conditioned place preference model. We observed that the lowest dose capable of promoting such aversion was 0.9%, which was used to induce pain in the following experiments. Experiment 2 aimed at determining the effects of MK-801 on the interaction with an animal in pain, regarding both the interaction ability itself and the reinforcing property promoted by such interaction. We observed that the control animals display longer interaction time with animals in pain and that this interaction promotes reinforcing effects, since it induces conditioned place preference. Treatment with MK-801 impairs both. Additionally, writhing in animals in pain are more pronounced when interacting with animals treated with MK-801 than when interacting with control animals. Experiments 3 and 4 were conducted to verify the effects of a typical and an atypical antipsychotic - haloperidol and clozapine, respectively - on the alterations found. Even though these antipsychotics did not improve the preference in interacting with a conspecific in pain, they did restore the rewarding effects of such interaction, being able to induce the development of preference for the compartment associated with interaction with an animal in pain. Our results point to the use of animal models for studying how social behaviors while watching an animal in pain and their reinforcing properties may be altered in schizophrenia, which could contribute to a better understanding of these deficits in schizophrenia, possible actions of antipsychotics, and the proposal of new therapeutic strategies for such impairments.
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    Interaction between glutamatergic-NMDA and cholinergic-muscarinic systems in classical fear conditioning
    (Elsevier B.V., 2008-09-30) Perez Figueredo, Larissa Zeggio [UNIFESP]; Moreira, Karin Monteiro [UNIFESP]; Ferreira, Tatiana Lima [UNIFESP]; Fornari, Raquel Vecchio [UNIFESP]; Menezes Oliveira, Maria Gabriela [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    A number of studies have suggested that the glutamatergic and cholinergic systems are both involved in learning and memory processes and that they interact in order to facilitate these processes. However, the role of M1-muscarinic receptors in mediating this interaction has not been elucidated.The aim of this study was to determine whether the concomitant administration of MK-801 (noncompetitive NMDA antagonist) and dicyclomine (M1-muscarinic antagonist - DIC) in sub-effective doses impairs contextual fear conditioning (hippocampal-dependent task) and tone fear conditioning tasks (hippocampal-independent task).The results showed that concomitant pre-training administration of DIC (8.0 mg/kg) and MK-801 (0.07 mg/kg) - two sub-effectives doses for the contextual fear conditioning task - does impair the performance of animals on this task (as measured by freezing behavior time). Tone fear conditioning tasks were not affected by the drugs either administered separately or concurrently.The pre-training administration of sub-effective doses of MK-801 and DIC in combination impairs performance on contextual fear conditioning task (hippocampal-dependent), but not on tone fear conditioning task (hippocampal-independent). These data support the hypothesis that the interaction between glutamatergic and cholinergic systems in hippocampus-dependent learning and memory processes probably occurs through M1 receptor. (C) 2008 Elsevier Inc. All rights reserved.
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    Interaction between M1-muscarinic and glutamatergic NMDA receptors on an inhibitory avoidance task
    (Elsevier B.V., 2005-11-30) Moreira, K. M.; Ferreira, T. L.; Fornari, R. V.; Figueredo, LZP; Oliveira, MGM; Universidade Federal de São Paulo (UNIFESP)
    It has been demonstrated that MK-801 potentiates the effects of the non-selective muscarinic antagonist scopolamine on memory in rats. in this study, we investigated the role of the M1-muscarinic receptor in this interaction, by administering different doses of dicyclomine (DIC) and MK-801 in combination to male Wistar rats before training on the inhibitory avoidance task. MK-801 and DIC in sub-effective doses were administered in combination. It was observed that MK-801 at a dose of 0.1125 mg/kg with a sub-effective dose of 8 mg/kg of DIC significantly impaired the retention test when compared with saline-treated animals, i.e. MK-801 potentiated the effects of dicyclomine on memory impairment. Our results suggest an important role for the M1-muscarinic receptor in the synergistic interaction between cholinergic muscarinic and glutamatergic NMDA receptors, which is in line with the findings that the interactive modulation between these two neurotransmitters systems constitutes an important mechanism in cognitive functions. (c) 2005 Elsevier Inc. All rights reserved.
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    MK-801 blocks the development of behavioral sensitization to ethanol
    (Lippincott Williams & Wilkins, 2000-03-01) Camarini, R.; Frussa, R.; Monteiro, M. G.; Calil, H. M.; Universidade Federal de São Paulo (UNIFESP)
    Background: Studies have indicated that MK-801 (a noncompetitive N-methyl-D-aspartate receptor antagonist) participates in the long-term neural changes responsible for sensitization to stimulant drugs. It is known that repeated administration of low doses of ethanol sensitizes animals to its stimulant effect. in this work we investigated whether MK-801 alters the development of behavioral sensitization to ethanol.Methods: Groups of male Swiss mice were treated with saline or ethanol (2.0 g/kg) plus saline or MK-801 (0.25 mg/kg) for 21 days. On day 25, all animals received an ethanol challenge injection (2.0 g/kg). We measured locomotor activity on days 1, 7, 14, 21 and 25. in addition, we assessed the effects of different doses of MK-801 on the response to a low dose of ethanol (2.0 g/kg).Results: Ethanol-treated mice developed sensitization to the locomotor-stimulating effect of the drug, whereas those concomitantly receiving ethanol and MK-801 did nut. All doses of MK-801 that were used stimulated the locomotor activity of both ethanol and saline-treated animals.Conclusions: the findings support the hypothesis that N-methyl-D-aspartate receptors have an important role in the development of sensitization to drugs of abuse.
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    Reciprocal interactions between MK-801, sleep deprivation and recovery in modulating rat behaviour
    (Elsevier B.V., 2011-01-01) Dubiela, Francisco Paulino [UNIFESP]; Messias, Melissa Fudoli [UNIFESP]; Moreira, Karin Di Monteiro [UNIFESP]; Zanlorenci, Lineane Helena Fernandes [UNIFESP]; Grassl, Christian [UNIFESP]; Frussa Filho, Roberto [UNIFESP]; Nobrega, Jose N.; Tufik, Sergio [UNIFESP]; Hipólide, Débora Cristina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Ctr Addict & Mental Hlth
    Increasing evidence indicates that sleep deprivation alters behavioural responses to various pharmacological agents which might be associated to changes in receptor systems. the present work addressed the effects of sleep deprivation and recovery on behavioural changes induced by MK-801, and investigated whether such effects are related to changes in NMDA receptor (NMDAR) binding. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24 h (SR group). Animals were treated with saline or 0.05, 0.10 or 0.20 mg/kg MK-801 before testing in an open field arena and elevated plus maze. A separate set of animals was sacrificed for [(3)H]MK-801 binding analysis in 40 brain regions. MK-801-induced hyperlocomotion was facilitated in a dose-dependent fashion after SR, while SD-induced increase in grooming was antagonized by the drug. Anxiolytic effects of 0.05 and 0.10 mg/kg MK-801 were unaffected by SD or SR conditions. No significant differences among groups were found in NMDAR binding. These findings indicate that the combined effects of MK-801 and sleep deprivation and recovery interact in a complex fashion to affect rat behaviour. They further suggest that such effects cannot be attributed to altered NMDAR binding in brain. (C) 2010 Elsevier B.V. All rights reserved.