Navegando por Palavras-chave "Modafinil"
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- ItemAcesso aberto (Open Access)Caracterização experimental da sensibilização comportamental "imediata" ao modafinil em camundongos(Universidade Federal de São Paulo (UNIFESP), 2015-02-28) Wuo-Silva, Raphael [UNIFESP]; Longo, Beatriz Monteiro [UNIFESP]; Frussa Filho, Roberto [UNIFESP]; Fukushiro, Daniela Fukue [UNIFESP]; http://lattes.cnpq.br/6272810367202712; http://lattes.cnpq.br/0245964878412260; http://repositorio.unifesp.br/handle/11600/37711; http://lattes.cnpq.br/1749698639669140; Universidade Federal de São Paulo (UNIFESP)Há grande controvérsia sobre o potencial de abuso do modafinil, uma droga aprovada para o tratamento da narcolepsia, estudada como possível agente terapêutico para o tratamento da dependência por cocaína, e utilizada de modo indiscriminado por indivíduos saudáveis devido aos seus efeitos benéficos sobre o alerta e a cognição. Uma forma de se estudar as alterações neuroplásticas que ocorrem rapidamente após a administração de drogas e que levam, consequentemente ao abuso destas, é por meio do modelo animal de sensibilização comportamental imediata, previamente caracterizado para a anfetamina em roedores. Nesse modelo, uma injeção de anfetamina em uma dose baixa foi capaz de eliciar comportamentos estereotipados e hiperlocomoção vigorosos quando administrada a roedores que haviam recebido uma única injeção de anfetamina apenas algumas horas antes. Sendo assim, essa Tese teve como objetivos: 1) validar e caracterizar comportamentalmente o fenômeno de sensibilização imediata ao modafinil em camundongos, 2) verificar a participação de receptores dopaminérgicos D1 e D2 no desenvolvimento da sensibilização imediata ao modafinil, 3) verificar o possível desenvolvimento de sensibilização comportamental imediata cruzada entre modafinil e cocaína e 4) verificar possíveis alterações na neurogênese hipocampal após a sensibilização imediata ao modafinil e a sensibilização imediata cruzada entre o modafinil e a cocaína. Como resultados, verificamos que o efeito estimulante locomotor da injeção indutora de modafinil cessou 150 minutos após a sua administração e que uma injeção indutora de modafinil na dose de 64 mg/kg induziu sensibilização comportamental imediata a injeções desafio de modafinil nas doses de 16 mg/kg, 32 mg/kg e 64 mg/kg, administradas 4 horas após a injeção indutora. Verificamos ainda que o antagonista D1 SCH 23390, mas não o antagonista D2 sulpiride, atenuou o efeito estimulante locomotor induzido pelo modafinil. No entanto, ambos os antagonistas dopaminérgicos inibiram a sensibilização comportamental imediata ao modafinil. Ainda, a sensibilização imediata também ocorreu de maneira cruzada e bidirecional entre o modafinil e a cocaína Por fim, a sensibilização imediata ao modafinil e a sensibilização imediata cruzada entre modafinil e cocaína não alteraram a neurogênese, avaliada pela quantificação de neurônios DCX+ no hipocampo. Tomados em conjunto, os presentes achados fornecem evidências pré-clínicas do potencial de abuso do modafinil, mostrando que essa droga é capaz de promover neuroadaptações praticamente imediatas, que envolvem a participação dos receptores dopaminérgicos D1 e D2, e que estão intimamente relacionadas aos mecanismos subjacentes à dependência de cocaína.
- ItemSomente MetadadadosDopamine transporter-related effects of modafinil in rhesus monkeys(Springer, 2010-06-01) Andersen, Monica L. [UNIFESP]; Kessler, Eileen; Murnane, Kevin S.; McClung, Jessica C.; Tufik, Sergio [UNIFESP]; Howell, Leonard L.; Emory Univ; Universidade Federal de São Paulo (UNIFESP)Modafinil is currently used as a treatment for daytime sleepiness.The objectives of this study were to explore the dopamine transporter (DAT)-related effects of modafinil on behavior and in vivo neurochemistry in rhesus monkeys (Macaca mulatta).The effects of modafinil (3.0-10 mg/kg, i.v.) were evaluated on locomotor activity, reinstatement of cocaine-maintained behavior, extracellular dopamine levels in the caudate nucleus, and DAT occupancy in the dorsal striatum. Eight subjects were fitted with a collar-mounted activity monitor to evaluate sleep-activity cycles, with 4 days of baseline recording preceding an injection of saline or modafinil (3.0-10 mg/kg). the effects of modafinil (3.0-10 mg/kg) and cocaine (0.3 mg/kg) on reinstatement of behavior that was previously maintained under a second-order schedule of i.v. cocaine delivery were tested in a separate group of subjects (n = 6). Finally, the effects of modafinil (3.0-10 mg/kg) on extracellular dopamine levels and DAT occupancy in vivo were characterized using microdialysis and positron emission tomography, respectively, in a within-subjects design (n = 4).Modafinil significantly increased nighttime locomotor activity and reinstated cocaine-maintained behavior but did not affect daytime locomotor activity. Modafinil significantly increased striatal extracellular dopamine levels at a dose that resulted in DAT occupancy of 64.4% (putamen) and 60.2% (caudate).The behavioral and in vivo dopaminergic effects of modafinil are consistent with the profile of a low potency DAT inhibitor and may indicate potential for abuse at high doses.
- ItemAcesso aberto (Open Access)Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats(Associação Brasileira de Divulgação Científica, 2008-01-01) Martins, Raquel Cristina Silva [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Shih, Ming Chi [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.
- ItemSomente MetadadadosIncreased interferon-mediated immunity following in vitro and in vivo Modafinil treatment on peripheral immune cells(Pergamon-Elsevier Science Ltd, 2018) Zager, Adriano; Brandao, Wesley Nogueira; Margatho, Rafael Oliveira; Gimenes Cruz, Daniel Sanzio; Peron, Jean Pierre; Tufik, Sergio [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Moresco, Monica; Pizza, Fabio; Plazzi, Giuseppe; Kornum, Birgitte Rahbek; Palermo-Neto, JoaoThe wake-promoting drug Modafinil has been used for treatment of sleep disorders, such as Narcolepsy, excessive daytime sleepiness and sleep apnea, due to its stimulant action. Despite the known effect of Modafinil on brain neurochemistry, particularly on brain dopamine system, recent evidence support an immunomodulatory role for Modafinil treatment in neuroinflammatory models. Here, we aimed to study the effects of in vitro and in vivo Modafinil treatment on activation, proliferation, cell viability, and cytokine production by immune cells in splenocytes culture from mice. The results show that in vitro treatment with Modafinil increased Interferon (IFN)-gamma, Interleukin (IL)-2 and IL-17 production and CD25 expression by T cells. In turn, in vivo Modafinil treatment enhanced splenocyte production of IFN-gamma, IL-6 and tumor necrosis factor (TNF), and increased the number of IFN-gamma producing cells. Next, we addressed the translational value of the observed effects by testing PBMCs from Narcolepsy type 1 patients that underwent Modafinil treatment. We reported increased number of IFN-gamma producing cells in PBMCs from Narcolepsy type 1 patients following continuous Modafinil treatment, corroborating our animal data. Taken together, our results show, for the first time, a pro-inflammatory action of Modafinil, particularly on IFN-mediated immunity, in mice and in patients with Narcolepsy type 1. The study suggests a novel effect of this drug treatment, which should be taken into consideration when given concomitantly with an ongoing inflammatory or autoimmune process.
- ItemSomente MetadadadosInhibitory effects of modafinil on emotional memory in mice(Elsevier B.V., 2013-01-01) Fernandes, Helaine A. [UNIFESP]; Zanin, Karina A. [UNIFESP]; Patti, Camilla L. [UNIFESP]; Wuo-Silva, Raphael [UNIFESP]; Carvalho, Rita C. [UNIFESP]; Fernandes-Santos, Luciano [UNIFESP]; Bittencourt, Lia R. A. [UNIFESP]; Tufik, Sergio [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Modafinil (MOD), a psychostimulant used to treat narcolepsy, excessive daytime sleepiness, and sleepiness due to obstructive sleep apnea, appears to promote a possible facilitatory effect on cognitive function. in the present study, we investigated the effects of the acute administration of MOD on the different steps of emotional memory formation and usage (acquisition, consolidation and retrieval) as well as the possible participation of the state-dependency phenomenon on the cognitive effects of this compound. Mice were acutely treated with 32, 64 or 128 mg/kg MOD before training or testing or immediately after training and were subjected to the plus-maze discriminative avoidance task. the results showed that although pre-training MOD administration did not exert any effects on learning, the doses of 32 or 64 mg/kg induced emotional memory deficits during testing. Still, the post-training acute administration of the higher doses of MOD (64 and 128 mg/kg) impaired associative memory consolidation. When the drug was administered pre-test, only the 32 mg/kg dose impaired the task retrieval. Importantly, the cognitive impairing effects induced by 32 mg/kg MOD were not related to the phenomenon of state-dependency. in all, our findings provide pre-clinical evidence of potential emotional memory amnesia induced by MOD.This article is part of a Special Issue entitled 'Cognitive Enhancers'. (C) 2012 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosModafinil ameliorates cognitive deficits induced by maternal separation and sleep deprivation(Elsevier B.V., 2013-09-15) Garcia, Vanessa Athaide [UNIFESP]; Hirotsu, Camila [UNIFESP]; Matos, Gabriela [UNIFESP]; Alvarenga, Tathiana [UNIFESP]; Pires, Gabriel Natan [UNIFESP]; Kapczinski, Flavio; Schroeder, Nadja; Tufik, Sergio [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Pontifical Catholic Univ; Natl Inst Translat Med INCT TM; Universidade Federal de São Paulo (UNIFESP); Univ Fed Rio Grande do SulAnimals exposed to an early adverse event may be more susceptible to a second source of stress later in life, and these stressors may have additive deleterious effects. Sleep deprivation is known to be a stressor, affecting multiple body functions such as the cognition. Modafinil enhances working memory and attention in healthy non-sleep deprived subjects and in animal models of sleep deprivation. the first aim of the present study was to investigate the effects of maternal separation (MS) combined with paradoxical sleep deprivation (PSD) in adulthood on recognition memory in rats. Second, we aimed to evaluate whether the administration of modafinil would be able to ameliorate memory deficits induced by MS and PSD. Wistar rat pups were initially distributed into MS and handling (H) groups, with their litters standardized in 4 females and 4 males. in adulthood, the male rats were submitted to PSD or control condition, being redistributed afterwards in modafinil- or vehicle-treatment immediately after the training session of object recognition task. PSD did not potentiate the cognitive deficit due to MS. However, modafinil was able to recover memory impairments associated to PSD and also to MS in the neonatal period. This study demonstrates for the first time that modafinil ameliorates cognitive deficits associated to MS and to PSD in adulthood, independent from MS in the neonatal period. (C) 2013 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosThe wake-promoting drug Modafinil prevents motor impairment in sickness behavior induced by LPS in mice: Role for dopaminergic D1 receptor(Pergamon-Elsevier Science Ltd, 2018) Zager, Adriano; Brandao, Wesley Nogueira; Margatho, Rafael Oliveira; Peron, Jean Pierre; Tufik, Sergio [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Kornum, Birgitte Rahbek; Palermo-Neto, JoaoThe wake-promoting drug Modafinil has been used for many years for treatment of Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related psychostimulant action. Recent studies have indicated that Modafinil prevents neuroinflammation in animal models. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced sickness and depressive-like behaviors. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil (90 mg/Kg) and, 30 min later, received a single saline or LPS (2 mg/Kg) administration, and were submitted to the open field and elevated plus maze test 2 h later. After 24 h, mice were subjected to tail suspension test, followed by either flow cytometry with whole brain for CD11b(+) CD45(+) cells or qPCR in brain areas for cytokine gene expression. Modafinil treatment prevented the LPS-induced motor impairment, anxiety-like and depressive-like behaviors, as well as the increase in brain CD11b(+) CD45(high) cells induced by LPS. Our results indicate that Modafinil pretreatment also decreased the IL-1 beta gene upregulation caused by LPS in brain areas, which is possibly correlated with the preventive behavioral effects. The pharmacological blockage of the dopaminergic D1R by the drug SCH-23390 counteracted the effect of Modafinil on locomotion and anxiety-like behavior, but not on depressive-like behavior and brain immune cells. The dopaminergic D1 receptor signaling is essential to the Modafinil effects on LPS-induced alterations in locomotion and anxiety, but not on depression and brain macrophages. This evidence suggests that Modafinil treatment might be useful to prevent inflammation-related behavioral alterations, possibly due to a neuroimmune mechanism.