采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动机效应。
Assessing the motivational effects of ethanol in mice using a discrete-trial current-intensity intracranial self-stimulation procedure.
机构信息
Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.
出版信息
Drug Alcohol Depend. 2020 Feb 1;207:107806. doi: 10.1016/j.drugalcdep.2019.107806. Epub 2019 Dec 16.
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.
背景
酒精（乙醇）既能产生奖赏作用，也能产生厌恶作用，而对这些作用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动机效应是 AUD 神经生物学基础的临床前研究中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）程序是否可用于评估乙醇对小鼠的奖赏增强和厌恶反应。
方法
雄性和雌性 C57BL/6J 小鼠接受双极刺激电极植入手术，以瞄准内侧前脑束，并在离散试验电流强度 ICSS 程序上进行训练。使用拉丁方设计，用各种剂量的乙醇（0.5 g/kg-1.75 g/kg；n = 5-7 个剂量）测试小鼠的反应阈值变化。
结果
1 g/kg 的乙醇剂量产生了显著的奖赏增强作用（即降低了反应阈值），而 1.75 g/kg 的乙醇剂量产生了厌恶作用（提高了反应阈值）。与生理盐水处理相比，1 至 1.75 g/kg 的乙醇剂量增加了反应潜伏期。
结论
离散试验电流强度 ICSS 程序是一种有效的测量方法，可用于测量乙醇的奖赏增强反应和相同动物中的厌恶反应。这将被证明是评估实验操作对小鼠乙醇动机效应的影响的有用工具。
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