Evaluation of anxiety-like behaviors following ethanol withdrawal in mice: effects of cannabidiol

Leticia Pin Coltri, V. T. Bonassoli, H. Milani, Rubia M W Oliveira
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Abstract

The abrupt interruption of ethanol consumption increases anxiety-like behaviors in rodents and may reflect different aspects of ethanol dependence in humans. Measuring emotional behaviors resulting from ethanol withdrawal may aid in testing potential pharmacological agents for the treatment of ethanol dependence. In the present study, we used forced expositon to ethanol 20% during 10 days to mice, followed by abrupt withdrawal of the substance. The animals were evaluated 7, 24 and 35 h after ethanol withdrawal in three different behavioral paradigms, i.e., the open field (OF), light dark (LD) transition and elevated plus maze (EPM), tests usually used to measure anxiety-like behaviors. This was done with the aim of identifying the best interval as well as the most appropriate behavioral test to detect the effects of drugs that can relieve anxiety induced by ethanol withdrawal in mice. We also evaluated the effect of cannabidiol (CBD 10, 30 and 60 mg kg) in ethanol withdrawn mice because it has been shown to alliviate drug addicton and present anti-anxiety effects. Our results show significant behavioral changes at 24 h following ethanol withdrawal. Diazepam (4 mg kg), used as a positive control, counteracted the effects of ethanol withdrawal in OF, LD box and EPM. Cannabidiol attenuated anxiety-like behavior produced at 24 h after abstinence from ethanol exposure only in the EPM test.
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对小鼠乙醇戒断后焦虑样行为的评价:大麻二酚的作用
乙醇消耗的突然中断增加了啮齿动物的焦虑样行为,可能反映了人类对乙醇依赖的不同方面。测量酒精戒断引起的情绪行为可能有助于测试治疗酒精依赖的潜在药理学药物。在本研究中,我们对小鼠进行了为期10天的20%乙醇强制暴露,然后突然退出该物质。在乙醇戒断后7、24和35 h,分别对动物进行开放场(OF)、明暗过渡(LD)和升高加迷宫(EPM)三种不同的行为模式的评估,这三种模式通常用于测量焦虑样行为。这样做的目的是确定最佳的间隔时间,以及最合适的行为测试,以检测药物的效果,可以缓解乙醇戒断引起的小鼠焦虑。我们还评估了大麻二酚(CBD 10、30和60 mg kg)对乙醇戒断小鼠的影响,因为它已被证明可以缓解药物成瘾并具有抗焦虑作用。我们的研究结果显示,在乙醇戒断后24小时,行为发生了显著变化。以地西泮(4 mg kg)作为阳性对照,可抵消乙醇对of、LD盒和EPM的影响。大麻二酚仅在EPM试验中减轻乙醇暴露戒断后24小时产生的焦虑样行为。
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