BACKGROUND Alcohol (ethanol) produces both rewarding and aversive effects, and sensitivity to these effects is associated with risk for an alcohol use disorder (AUD). Measurement of these motivational effects in animal models is an important but challenging aspect of preclinical research into the neurobiology of AUD. Here, we evaluated whether a discrete-trial current-intensity intracranial self-stimulation (ICSS) procedure can be used to assess both reward-enhancing and aversive responses to ethanol in mice. METHODS Male and female C57BL/6J mice were surgically implanted with bipolar stimulating electrodes targeting the medial forebrain bundle and trained on a discrete-trial current-intensity ICSS procedure. Mice were tested for changes in response thresholds after various doses of ethanol (0.5 g/kg-1.75 g/kg; n = 5-7 per dose), using a Latin square design. RESULTS A 1 g/kg dose of ethanol produced a significant reward-enhancement (i.e., lowered response thresholds), whereas a 1.75 g/kg dose produced an aversive effect (elevated response thresholds). Ethanol doses from 1 to 1.75 g/kg increased response latencies as compared to saline treatment. CONCLUSIONS The discrete-trial current-intensity ICSS procedure is an effective assay for measuring both reward-enhancing responses to ethanol as well as aversive responses in the same animal. This should prove to be a useful tool for assessing the effects of experimental manipulations on the motivational effects of ethanol in mice.

中文翻译：

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使用离散试验电流强度颅内自我刺激程序评估乙醇对小鼠的刺激作用。

背景技术酒精（乙醇）产生有益和厌恶的效果，并且对这些效果的敏感性与酒精使用障碍（AUD）的风险相关。在动物模型中测量这些激励作用是AUD神经生物学的临床前研究的一个重要但具有挑战性的方面。在这里，我们评估了离散试验电流强度颅内自我刺激（ICSS）程序是否可以用于评估小鼠对乙醇的奖励增强和厌恶反应。方法雄性和雌性C57BL / 6J小鼠均通过外科手术植入靶向前脑内侧束的双极刺激电极，并接受离散试验电流强度ICSS程序训练。在不同剂量的乙醇（0.5 g / kg-1.75 g / kg； n = 5-7每剂量）后，测试小鼠的反应阈值变化，使用拉丁方形设计。结果1 g / kg剂量的乙醇产生显着的奖励增强（即降低的反应阈值），而1.75 g / kg剂量的乙醇产生厌恶作用（升高的反应阈值）。与生理盐水处理相比，乙醇剂量为1至1.75 g / kg可以增加响应潜伏期。结论离散试验电流强度ICSS程序是一种有效的测定方法，用于测量同一只动物对乙醇的奖励增强反应以及厌恶反应。这应该被证明是评估实验操作对乙醇对小鼠的激励作用的影响的有用工具。75 g / kg剂量产生厌恶效果（升高的反应阈值）。与生理盐水处理相比，乙醇剂量为1至1.75 g / kg可以增加响应潜伏期。结论离散试验电流强度ICSS程序是一种有效的测定方法，用于测量同一只动物对乙醇的奖励增强反应以及厌恶反应。这应该被证明是评估实验操作对乙醇对小鼠的激励作用的影响的有用工具。75 g / kg剂量产生厌恶效果（升高的反应阈值）。与生理盐水处理相比，乙醇剂量为1至1.75 g / kg可以增加响应潜伏期。结论离散试验电流强度ICSS程序是一种有效的测定方法，用于测量同一只动物对乙醇的奖励增强反应以及厌恶反应。这应该被证明是评估实验操作对乙醇对小鼠的激励作用的影响的有用工具。