Department of Psychobiology, University of Valencia, Valencia, Spain.
Department of Psychology, Universidad Internacional de Valencia, Valencia, Spain.
Behav Brain Res. 2020 Mar 2;381:112457. doi: 10.1016/j.bbr.2019.112457. Epub 2019 Dec 28.
The Binge Drinking (BD) pattern of alcohol consumption, prevalent in adolescents and young adults, has been associated with memory impairment. In addition, evidence shows that alcohol abuse causes neuroinflammation, which may contribute to the brain damage produced by alcohol and explain its cognitive consequences. In this study, we evaluated the effectiveness of the anti-inflammatory indomethacin in counteracting the memory impairment produced by alcohol (ethanol) in adolescent mice of both sexes. Animals were randomly assigned to one of four groups for each sex: SS (saline + saline), SA (saline + alcohol), SI (saline + indomethacin) and AI (alcohol + indomethacin). They were injected acutely (Experiment 1) or chronically intermittent (Experiment 2) with saline, ethanol (3 g/kg) and indomethacin (10 mg/kg). All subjects were evaluated in an inhibitory avoidance task 96 h after treatment. With acute administration, SA groups showed significantly lower Test latencies than SS groups, while AI groups had similar latencies to controls. The chronic-intermittent administration of alcohol, an animal model of BD, produced significant emotional memory impairment -blocking learning in males- which was counteracted by indomethacin, as the AI groups had similar latencies to the SS groups. No significant differences were observed in locomotor activity or analgesia. In conclusion, alcohol BD (one or several episodes) impairs emotional memory in mice. This impairment is not secondary to the effects of alcohol BD on locomotor activity or pain sensitivity, and it is counteracted by indomethacin. Therefore, the memory impairment produced by alcohol BD seems to be mediated, in part, by neuroinflammatory processes. These findings open a window for new treatments for alcohol use disorders.
binge drinking（BD）是一种在青少年和年轻人中普遍存在的饮酒模式，与记忆障碍有关。此外，有证据表明，酒精滥用会引起神经炎症，这可能导致酒精引起的大脑损伤，并解释其认知后果。在这项研究中，我们评估了抗炎药吲哚美辛在对抗酒精（乙醇）对青少年雌雄小鼠产生的记忆障碍的有效性。动物被随机分为雌雄各四组：SS（生理盐水+生理盐水）、SA（生理盐水+酒精）、SI（生理盐水+吲哚美辛）和 AI（酒精+吲哚美辛）。它们分别接受了急性（实验 1）或慢性间歇性（实验 2）的生理盐水、乙醇（3g/kg）和吲哚美辛（10mg/kg）注射。所有动物在治疗后 96 小时接受抑制性回避任务评估。在急性给药时，SA 组的测试潜伏期明显低于 SS 组，而 AI 组的潜伏期与对照组相似。BD 动物模型的慢性间歇性酒精给药导致明显的情绪记忆障碍-阻断雄性的学习能力-吲哚美辛可拮抗该障碍，因为 AI 组的潜伏期与 SS 组相似。在运动活动或镇痛方面未观察到显著差异。总之，BD 酒精（一次或多次发作）会损害小鼠的情绪记忆。这种损害不是由于 BD 酒精对运动活动或疼痛敏感性的影响引起的，并且吲哚美辛可拮抗该损害。因此，BD 酒精引起的记忆障碍似乎部分是由神经炎症过程介导的。这些发现为酒精使用障碍的新治疗方法开辟了一个窗口。
