Navegando por Palavras-chave "Rimonabant"

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    Effects of rimonabant on the development of single dose-induced behavioral sensitization to ethanol, morphine and cocaine in mice
    (Elsevier B.V., 2015-04-03) Marinho, Eduardo Ary Villela; Oliveira-Lima, Alexandre Justo de; Santos, Renan dos [UNIFESP]; Hollais, André Willian [UNIFESP]; Baldaia, Marilia Araujo [UNIFESP]; Wuo-Silva, Raphael [UNIFESP]; Yokoyama, Thais Suemi [UNIFESP]; Takatsu-Coleman, André Luis [UNIFESP]; Patti, Camilla de Lima [UNIFESP]; Longo, Beatriz Monteiro [UNIFESP]; Berro, Laís Fernanda [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Univ Estadual Santa Cruz UESC; Universidade Federal de São Paulo (UNIFESP)
    Rationale: the endocannabinoid system has been implicated in the neurobiological mechanism underlying drug addiction, especially the primary rewarding dopamine-dependent processes. Therefore, endocannabinoid receptor antagonists, such as the CB1 cannabinoid antagonist rimonabant, have been proposed as candidates for preventive addiction therapies.Objectives: Investigate the possible involvement of CB1 receptors in the development of behavioral sensitization to ethanol, morphine and cocaine in mice.Methods: We compared the effects of different doses of rimonabant (0.3, 1, 3 and 10 mg/kg) on spontaneous locomotor activity in the open-field, hyperlocomotion induced by acute administration of ethanol (1.8 g/kg), morphine (20 mg/kg) or cocaine (10 mg/kg) and on subsequent drug-induced locomotor sensitization using a two-injection protocol in mice. We also investigated a possible depressive-like effect of an acute rimonabant challenge at the highest dose and its potential anxiogenic property.Results: At the highest dose, rimonabant abolished ethanol-and cocaine-induced hyperlocomotion and behavioral sensitization without modifying spontaneous and central locomotor activity or inducing depressive-like behavior on the forced swim test in mice. the other doses of rimonabant also selectively blocked acute ethanol-induced central hyperlocomotion. Although rimonabant at 0.3 and 1 mg/kg potentiated the central hyperlocomotion induced by acute morphine injection, it was effective inattenuating morphine-induced behavioral sensitization at all doses.Conclusions: Because the neural basis of behavioral sensitization has been proposed to correspond to some components of addiction, our findings indicate that the endocannabinoid system might be involved in ethanol, cocaine and morphine abuse. (C) 2014 Elsevier Inc. All rights reserved.
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    Post-sensitization treatment with rimonabant blocks the expression of cocaine-induced behavioral sensitization and c-Fos protein in mice
    (Pergamon-Elsevier Science Ltd, 2017) Marinho, Eduardo Ary Villela; Oliveira-Lima, Alexandre Justo de; Yokoyama, Thais Suemi [UNIFESP]; Santos-Baldaia, Renan [UNIFESP]; Ribeiro, Luciana Takahashi Carvalho [UNIFESP]; Baldaia, Marilia Araujo [UNIFESP]; Wuo-Silva, Raphael [UNIFESP]; Hollais, André Willian [UNIFESP]; Talhati, Fernanda [UNIFESP]; Longo, Beatriz Monteiro [UNIFESP]; Berro, Laís Fernanda [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]
    CB1 receptor antagonists have been shown to prevent acute and long-term behavioral effects of cocaine. Here we evaluate the effectiveness of the CB1 receptor antagonist rimonabant to modify sensitized responses to cocaine. Mice were treated with saline or cocaine injections in a 15-day intermittent sensitization treatment and subsequently treated with either vehicle, 1 or 10 mg/kg rimonabant in the drug-associated environment for 8 consecutive days. Animals were then challenged with saline and cocaine in the open-field apparatus on subsequent days to evaluate the expression of conditioned and sensitized effects to cocaine. c-Fos protein expression was evaluated in the nucleus accumbens (NAcc), ventral tegmental area (VTA), basolateral amygdala (BLA), medial prefrontal cortex (mPFC) and caudate-putamen (CPu) after the last (cocaine) challenge. Previous treatment with 10 mg/kg rimonabant blocked the expression of conditioned hyperlocomotion and behavioral sensitization to cocaine, but not acute cocaine-induced hyperlocomotion. These behavioral effects were accompanied by significant changes in c-Fos expression in the brain reward system. Chronic cocaine sensitization blunted a subsequent acute cocaine-induced increase in c-Fos protein in the NAcc, effect that was reversed by previous treatment with rimonabant. Treatment with 10 mg/kg rimonabant also attenuated the significant increase in c-Fos expression in the CPu, mPFC and BLA induced by previous chronic sensitization with cocaine. Our findings add to the evidence that drugs targeting CB1 receptors are good candidates for the treatment of cocaine abuse and provide further insights into the mechanisms underlying endocannabinoid signaling within the brain reward system in the context of cocaine abuse.