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- ItemSomente MetadadadosMorphine attenuates the expression of sensitization to ethanol, but opioid antagonists do not(Elsevier B.V., 2008-10-28) Abrahao, Karina Possa [UNIFESP]; Quadros, I. M.; Souza-Formigoni, M. L. O. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Tufts UnivBehavioral sensitization to ethanol is characterized by an increased locomotor activity after repeated exposure. A great variability exists among species and strains in the development of sensitization. There is a growing amount of evidence to indicate that the opioid system is involved in alcoholism; it is possible, therefore, that this system also modulates the sensitization to ethanol. in this study we evaluated the role of the opioid system in determining the variability of the sensitized response to ethanol. Mice received repeated administrations of ethanol (2.2 g/kg) or saline every other day for 10 days. According to their locomotor response on the last day of treatment, ethanol-treated animals were classified into two groups: sensitized or non-sensitized mice. After the treatment, mice were submitted to four challenges 48 h apart. in experiments 1 and 2, mice were challenged, respectively, with i.p. administration of opioid antagonists (naloxone or naltrexone) or an opioid agonist (morphine), followed immediately by 2.2 g/kg ethanol. in experiment 3, animals received morphine by i.c.v., followed by 2.2 g/kg of ethanol (i.p.). Pretreatment with opioid antagonists (naloxone or naltrexone) did not block the expression of ethanol sensitization; however pretreatment with morphine attenuated the increased locomotor activity after ethanol administration in sensitized mice. in experiment 4, after the ethanol or saline treatment, mice brains were processed and brain mu opioid binding was assessed by autoradiography using [3H]D-Ala2,N-mePhe4, Gly-ol5-enkephalin ([3H]DAMGO). No differences were seen between any of the groups of mice, so the agonist effect is not likely to be mediated by differences in binding to mu opioid receptors. (C) 2008 IBRO. Published by Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosNaltrexone potentiates both amnestic and anxiolytic effects of chlordiazepoxide in mice(Elsevier B.V., 2002-12-27) Silva, R. H.; Frussa, R.; Universidade Federal de São Paulo (UNIFESP)Studies have suggested that opioid antagonists potentiate the anxiolytic effect but not the amnestic action of chlordiazepoxide (CDZ). We investigated the effects of naltrexone (NAL) on the anxiolytic and amnestic effects of CDZ in mice tested in the plus-maze discriminative avoidance task (DAT). Mice are conditioned to choose between two enclosed arms (one of which aversive) while avoiding the two open arms of the apparatus. This task measures memory (time spent in the aversive vs. time in the non-aversive enclosed arms) and anxiety (time spent in the open arms). Mice treated with saline (SAL) or 5 mg/kg NAL, and SAL or 2.5 mg/kg CDZ were submitted to DAT training. the test was performed 24 h later, without aversive stimuli. in the training, NAL + CDZ group showed higher percent time spent in the open arms than all the other groups. in the test, NAL + CDZ (but not SAL + CDZ) group showed higher percent time spent in the aversive enclosed arm than SAL + SAL and NAL + SAL groups. the data suggest that NAL potentiates the small decreases in anxiety and retention induced by a subeffective dose of CDZ. (C) 2002 Elsevier Science Inc. All rights reserved.
- ItemSomente MetadadadosNaltrexone potentiates the anxiolytic effects of chlordiazepoxide in rats exposed to novel environments(Springer, 1999-11-01) Frussa-Filho, R.; Barbosa-Junior, H.; Silva, R. H.; Da Cunha, C.; Mello, C. F.; Universidade Federal de São Paulo (UNIFESP); Univ Fed Parana; Universidade Federal de Sergipe (UFS)Rationale: Both novelty and naloxone have been reported to modify the anxiolytic-like effect of benzodiazepines in the elevated plus maze. in addition, it has been largely demonstrated that novelty alters endogenous opioid activity. Objectives: the present study was designed to examine a possible interaction between novelty and naltrexone effects on the behavior of chlordiazepoxide-treated rats in two animal models of anxiety. Methods: Thirty minutes after acute intraperitoneal treatment with saline or naltrexone and saline or chlordiazepoxide, male Wistar rats were exposed for the first time to the elevated plus maze apparatus or the social interaction arena for the quantification of the percentage of time spent in the open arms or the time of active social interaction, respectively. the effects of naltrexone and/or chlordiazepoxide on the plus maze and the social interaction tests were also evaluated after previous exposure to the respective apparatus. Results: Naltrexone dose dependently increased the percentage of time spent in the open arms of the elevated plus maze in chlordiazepoxide-treated (5 mg/kg i.p.) rats exposed for the first time to the apparatus. Similarly, naltrexone (5 mg/kg i.p.) increased the time spent in active social interaction by chlordiazepoxide-treated rats exposed to an unfamiliar arena. in both experiments, naltrexone had no effect when administered alone. When both the plus maze and the social interaction tests were conducted after previous exposure to the respective apparatus, naltrexone did not modify the behavior of chlordiazepoxide- or saline-treated rats. Conclusions: These data suggest that the anxiolytic-like effects of chlordiazepoxide can be modified by opioid mechanisms in navel environments.