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Evaluation of the effect of doxasozin and zonisamide on voluntary ethanol intake in mice that experienced chronic intermittent ethanol exposure and stress.
Alcohol ( IF 2.3 ) Pub Date : 2020-07-24 , DOI: 10.1016/j.alcohol.2020.07.005
Marcelo F Lopez 1 , Sarah E Reasons 1 , Benjamin A Carper 2 , Tracy L Nolen 2 , Rick L Williams 2 , Howard C Becker 3
Affiliation  

The comorbidity between alcohol use disorder and post-traumatic stress disorder represents a serious health care burden with few effective treatment options. The current study was designed to evaluate the effect of an alpha 1 receptor antagonist (doxazosin) and a novel anticonvulsant (zonisamide) in a model of alcohol (ethanol) dependence and stress exposure. The main dependent variable was voluntary ethanol intake in mice that experienced chronic intermittent ethanol (CIE) exposure and forced swim stress (FSS) alone, and in combination. Adult male and female C57BL/6J mice had access to a single bottle of 15% (v/v) ethanol for 1-hr in the home cage, 3-hr into the dark phase of the light/dark cycle. Once stable ethanol intake was established (~4 weeks), mice were separated into four groups (CTL, CIE, FSS, CIE + FSS). Mice in the FSS condition received 10-min FSS exposure 4-hr prior to drinking sessions (remaining mice were not disturbed). During baseline and the first two test cycles, all mice received vehicle (saline) injections (IP) 30-min before ethanol access. As previously observed, FSS increased ethanol drinking in dependent (CIE-exposed) mice but not in nondependent control (CTL) mice. In the following test cycles mice were evaluated for ethanol intake after administration of doxazosin, zonisamide or their combination. Results indicated that the three doses of doxazosin evaluated significantly reduced voluntary ethanol intake in all mice. Zonisamide had a more modest effect and may require a more prolonged treatment regime. The combined administration of both compounds was not more effective than each drug alone. This study suggests that doxazosin is reliable at reducing voluntary ethanol intake in mice independently of their history of ethanol dependence and stress exposure.



中文翻译:

评估多沙索嗪和唑尼沙胺对经历慢性间歇性乙醇暴露和应激的小鼠自愿乙醇摄入的影响。

酒精使用障碍和创伤后应激障碍之间的共病带来了严重的医疗负担,而且有效的治疗选择很少。目前的研究旨在评估α1受体拮抗剂(多沙唑嗪)和新型抗惊厥药(唑尼沙胺)在酒精(乙醇)依赖和压力暴露模型中的作用。主要因变量是单独或组合经历慢性间歇性乙醇(CIE)暴露和强迫游泳应激(FSS)的小鼠的自愿乙醇摄入量。成年雄性和雌性 C57BL/6J 小鼠在笼子中使用一瓶 15% (v/v) 乙醇 1 小时,进入光/暗循环的黑暗阶段 3 小时。一旦建立稳定的乙醇摄入量(约 4 周),将小鼠分为四组(CTL、CIE、FSS、CIE + FSS)。FSS 条件下的小鼠在饮酒前 4 小时接受 10 分钟的 FSS 暴露(其余小鼠不受干扰)。在基线和前两个测试周期中,所有小鼠在使用乙醇前 30 分钟接受赋形剂(盐水)注射 (IP)。正如之前所观察到的,FSS 增加了依赖性(CIE 暴露)小鼠的乙醇摄入量,但不增加非依赖性对照(CTL)小鼠的乙醇摄入量。在接下来的测试周期中,在给予多沙唑嗪、唑尼沙胺或其组合后,评估小鼠的乙醇摄入量。结果表明,三种剂量的多沙唑嗪显着减少了所有小鼠的自愿乙醇摄入量。唑尼沙胺的作用较温和,可能需要更长时间的治疗方案。两种化合物的联合给药并不比单独使用每种药物更有效。

更新日期:2020-09-07
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