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青少年 Sprague-Dawley 大鼠自愿性乙醇摄入增加:程序贡献和年龄特异性。

Voluntary elevated ethanol consumption in adolescent Sprague-Dawley rats: Procedural contributors and age-specificity.

机构信息

Binghamton University, Binghamton, NY, 13902, United States.

Binghamton University, Binghamton, NY, 13902, United States.

出版信息

Alcohol. 2019 Aug;78:1-12. doi: 10.1016/j.alcohol.2019.02.003. Epub 2019 Feb 22.

Abstract

Alcohol consumption is typically initiated during adolescence, with the incidence of binge drinking (production of blood ethanol concentrations [BECs] > 80 mg/dL) peaking during this stage of development. Studies in outbred rats investigating the consequences of adolescent ethanol exposure have typically employed intragastric, vapor, or intraperitoneal administration to attain BECs in this range. While these procedures have yielded valuable data regarding the consequences of adolescent exposure, they are varyingly stressful, administer the full dose at once, and/or bypass digestion. Consequently, we have worked to develop a model of voluntary elevated ethanol consumption in outbred adolescent Sprague-Dawley males and females, building on our previous work (see Hosová & Spear, 2017). This model utilizes daily 30-min access to 10% ethanol (v/v) in chocolate Boost® from postnatal day (P)28-41. Experiment 1 compared intake levels between (1a) animals given either ball-bearing or open-ended sipper tube tips for solution access, (1b) animals separated from their cage mate by wire mesh or isolated to a separate cage during solution access, (1c) animals given solution access with or without simultaneous access to banana-flavored sugar pellets, and (1d) animals that were either moderately food-restricted or fed ad libitum. Experiment 2 compared intake levels between animals given daily solution access and animals given access only on a "Monday-Wednesday-Friday" intermittent schedule. Experiment 3 compared adolescent and adult (P70-83) consumption using the finalized procedure as based on the results of Experiments 1 and 2. As in our previous work, consumptions well within the binge range were produced on some days, with high-consumption days typically followed by several days of lower consumption before increasing again. Sipper tube type (1a) and simultaneous pellet access (1c) did not affect consumption, while intake was significantly higher in non-isolated (1b), food-restricted (1d), daily-access (2), and adolescent (3) animals. However, although ethanol intake was higher in food-restricted animals, the resulting BECs were equivalent or higher in non-restricted animals, likely due to a hepatoprotective effect of moderate food restriction. Post-consumption intoxication ratings correlated with BECs and were notably higher in adults than adolescents, despite the lower voluntary consumption levels of adults, confirming prior reports of the attenuated sensitivity of adolescents to ethanol intoxication relative to adults. The final model utilized ball-bearing sipper tube tips to provide daily access to 10% ethanol in chocolate Boost® to free-feeding adolescent animals separated from their cage mate by wire mesh, with no food provided during solution access. This easy-to-implement model is effective in producing elevated voluntary ethanol consumption in adolescent, but not adult, Sprague-Dawley rats.

摘要

酒精消费通常始于青少年时期,狂饮(血液乙醇浓度[BEC] > 80mg/dL)的发生率在这一发育阶段达到高峰。在杂交大鼠中研究青少年期乙醇暴露的后果的研究通常采用胃内、蒸气或腹腔内给药来达到这一范围的 BEC。虽然这些程序产生了关于青少年暴露后果的有价值的数据,但它们是有压力的,一次给予全剂量,并且/或者绕过消化。因此,我们致力于开发一种杂交青少年雄性和雌性 Sprague-Dawley 大鼠自愿性升高乙醇消耗的模型,该模型建立在我们之前的工作基础上(见 Hosová & Spear,2017)。该模型利用从出生后第 28-41 天开始每天 30 分钟接触 10%乙醇(v/v)的巧克力 Boost®。实验 1 比较了(1a)给予球轴承或开口式吸管尖端用于溶液接触的动物、(1b)溶液接触期间通过金属丝网格与笼内同伴分离或单独隔离到单独笼子的动物、(1c)给予溶液接触同时给予香蕉味糖丸或不给予溶液接触的动物、(1d)给予适度食物限制或自由喂食的动物之间的摄入水平。实验 2 比较了每天给予溶液接触的动物和仅在“周一-周三-周五”间歇方案中给予溶液接触的动物之间的摄入水平。实验 3 使用根据实验 1 和 2 的结果确定的最终方案比较了青少年和成年(P70-83)的消耗情况。与我们之前的工作一样,在某些日子里产生了远高于狂饮范围的消耗,高消耗日通常伴随着几天的低消耗,然后再次增加。吸嘴管类型(1a)和同时给予糖丸(1c)不影响消耗,而非隔离(1b)、食物限制(1d)、每日接触(2)和青少年(3)动物的摄入明显更高。然而,尽管限制食物的动物的乙醇摄入量较高,但非限制动物的 BEC 相当或更高,这可能是由于适度食物限制的肝保护作用。消耗后中毒评分与 BEC 相关,且在成年动物中明显高于青少年动物,尽管成年动物的自愿消耗水平较低,这证实了先前关于青少年对乙醇中毒的敏感性低于成年动物的报告。最终模型利用球轴承吸嘴管尖端向通过金属丝网格与笼内同伴分离的自由喂养的青少年动物提供每日巧克力 Boost®中 10%乙醇的接触,溶液接触期间不提供食物。这种易于实施的模型可有效提高青少年但不是成年 Sprague-Dawley 大鼠的自愿性升高乙醇消耗。

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