Navegando por Palavras-chave "modafinil"
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- ItemSomente MetadadadosAddictive potential of modafinil and cross-sensitization with cocaine: a pre-clinical study(Wiley-Blackwell, 2011-10-01) Wuo-Silva, Raphael [UNIFESP]; Fukushiro, Daniela F. [UNIFESP]; Borcoi, Aline R. [UNIFESP]; Fernandes, Helaine A. [UNIFESP]; Procopio-Souza, Roberta [UNIFESP]; Hollais, Andre W. [UNIFESP]; Santos, Renan [UNIFESP]; Ribeiro, Luciana T. C. [UNIFESP]; Correa, Jussara M. R. M. [UNIFESP]; Talhati, Fernanda [UNIFESP]; Saito, Luis P. [UNIFESP]; Aramini, Tatiana C. F. [UNIFESP]; Kameda, Sonia R. [UNIFESP]; Bittencourt, Lia R. A. [UNIFESP]; Tufik, Sergio [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Repeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine.
- ItemAcesso aberto (Open Access)Fatores envolvidos no desenvolvimento e expressão da sensibilização comportamental ao efeito estimulante do modafinil e metanfetamina(Universidade Federal de São Paulo (UNIFESP), 2010-04-28) Soeiro, Aline da Costa [UNIFESP]; Oliveira, Maria Gabriela Menezes de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The behavioral sensitization refers to the progressive increase of the stimulatory effect induced by repeated administration of drugs of abuse such as cocaine and amphetamine. Previous studies suggest that the environment paired with the drug stimulant effect of those drugs has an important role in the behavioral sensitization phenomena. Besides, the chronic treatment with one drug of abuse can induce a different patter of response to the administration of other drug indicating that both drug share some similar mechanism of action. The present study aimed to investigate the involvement of contextual learning in the modafinil and methamphetamine behavioral sensitization phenomena and if there is cross-sensitization between the two drugs. Fifteen days after the contextual fear conditioning task, mice received repeated administration of vehicle or modafinil (50mg/kg - Experiment 2) and saline or methamphetamine (1mg/kg - Experiment 3) for 10 days; they were tested in activity cages on days 1, 5 and 10. To evaluate the expression of behavioral sensitization the mice were challenged with vehicle or modafinil (50mg/kg - Experiment 2) and saline or methamphetamine (1 mg/kg - Experiment 3) and then they were tested in the activity cages and in the open field arena. For cross-sensitization test, mice from Experiment 2 were challenged with saline and methamphetamine (1mg/kg) and those mice from Experiment 3 were challenged with vehicle and modafinil (50mg/kg). In both experiments we did not find any correlation between the levels of freezing in the contextual fear conditioning task and different levels of sensitization. Modafinil-sensitized subgroup of mice expressed clear behavioral sensitization in the activity cage, but not in the open field, suggesting a context-dependent expression of modafinil sensitization. We also observed a symmetric cross-sensitization between modafinil and methamphetamine. Our findings indicate that there are a important individual variability to the development of behavioral sensitization to methamphetamine and to modafinil. Besides, we suggest that modafinil and methamphetamine seem to share similar mechanisms of action.
- ItemSomente MetadadadosModafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil(Frontiers Media Sa, 2016) Wuo-Silva, Raphael [UNIFESP]; Fukushiro, Daniela Fukue [UNIFESP]; Hollais, André Willian [UNIFESP]; Santos-Baldaia, Renan [UNIFESP]; Mari-Kawamoto, Elisa [UNIFESP]; Berro, Laís Fernanda [UNIFESP]; Yokoyama, Thais Suemi [UNIFESP]; Lopes-Silva, Leonardo Brito [UNIFESP]; Bizerra, Carolina Souza [UNIFESP]; Procopio-Souza, Roberta [UNIFESP]; Hashiguchi, Debora [UNIFESP]; Figueiredo, Lilian A. [UNIFESP]; Costa, Jose L.; Frussa-Filho, Roberto [UNIFESP]; Longo, Beatriz Monteiro [UNIFESP]There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.
- ItemSomente MetadadadosPlacebo and modafinil effect on sleepiness in obstructive sleep apnea(Elsevier B.V., 2008-02-15) Bittencourt, Lia Rita A. [UNIFESP]; Lucchesi, Ligia M. [UNIFESP]; Rueda, Adriana D. [UNIFESP]; Garbuio, Silvério Aparecido [UNIFESP]; Palombini, Luciana O. [UNIFESP]; Guilleminault, Christian; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Stanford UnivIntroduction: Previous studies have evaluated the effect of modafinil on residual excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome (OSAS) under effective CPAP treatment. Even though those trials also used placebo groups, we suppose that the placebo effect might influence the patients' response to modafinil.Methods: Twenty sleepy patients with OSAS under CPAP treatment were selected. All of them had Epworth Sleepiness Scale (ESS) > 10. Following baseline evaluation (T1), all subjects were instructed to take placebo for 7 days. After this single-blind placebo phase and second evaluation (T2), patients were randomly allocated to placebo or modafinil treatment for 21 days in a double-blind protocol. Patients underwent a final evaluation (T3) on the last day of drug intake. the evaluations at T1, T2 and T3 consisted of. medical and laboratory examinations, nocturnal polysomnography, ESS, maintenance of wakefulness test (MWT) and complex reaction time (CRT-NY). in addition, in T2 and T3 the change of illness severity scale (CGI-C) and the evaluation of quality of life. (SF-36) were applied.Results: the comparison between the two groups during the three periods studied, showed the following results: in the modafinil group, ESS score did not change during the initial placebo period, but there was a significant reduction during the modafinil treatment period (p=0.0006); in the placebo group a significant reduction occurred during the initial placebo period (p=0.05), and no further change was observed in the treatment (placebo) period. A significant difference was found between the two groups after the placebo period (T2) (p=0.02). Three patients (33%) of the modafinil group and 9 patients (81%) of the placebo group were classified as placebo-responsive (X-2 : p=0.039). in the treatment period, reaction time was significantly reduced in the modafinil group compared to the placebo group (p<0.02). There was a trend toward improvement in overall clinical condition and also in some domains of SF-36 in the modafinil group.Conclusion: in summary, our study confirms that modafinil used adjunctively with CPAP therapy improves subjective daytime sleepiness in patients with OSAS who were regular users of CPAP therapy but still experienced sleepiness. Moreover, it could help in the improvement of objective measures of behavioral alertness and reduce functional impairments. the usefulness of a blinded placebo period for systematic investigation of placebo role in studies based on subjective response is a point that should be considered in this type of drug trial. (c) 2007 Elsevier Inc. All rights reserved.