Department of Pharmacology, Isfahan Pharmaceutical Sciences Research Centre, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran.
Eur J Pharmacol. 2012 Nov 15;695(1-3):83-7. doi: 10.1016/j.ejphar.2012.08.022. Epub 2012 Sep 7.
Effects of the nimodipine, L-type calcium channel antagonist, has been studied on memory loss caused by spontaneous morphine withdrawal in mice. Mice were made dependent by increasing doses of morphine over three days. Memory was evaluated using object recognition task, which is based on tendency of rodents to exploration of new objects. The test was comprised of three sections: 15 min habitation, 12 min first trial and 5 min test trial. Recognition index was evaluated 4h after the last dose of morphine. Nimodipine was administrated either in chronic form (1, 5 and 10mg/kg) with daily doses of morphine or it was given as a single injection (5 and 10mg/kg) on the last day. Nimodipine in both treatment forms prevented the memory impairment following spontaneous morphine withdrawal. Corticosterone concentration was increased in brain and blood of mice during abstinence phase and pretreatment with nimodipine prevented the increase in brain and blood corticosterone concentration. The results show that blockade of L-type calcium channels improves memory deficits caused by morphine withdrawal. This indicates that some kind of treatments, such as nimodipine, administrated over the acute withdrawal phase, can prevent memory deficit during withdrawal.
尼莫地平(L 型钙通道拮抗剂)对自发吗啡戒断引起的小鼠记忆缺失的影响。小鼠通过三天增加吗啡剂量来依赖。使用基于啮齿动物探索新物体倾向的物体识别任务来评估记忆。该测试由三个部分组成:15 分钟适应期、12 分钟第一次试验和 5 分钟测试试验。在最后一次吗啡给药后 4 小时评估识别指数。尼莫地平以慢性形式(1、5 和 10mg/kg)与每日吗啡剂量一起给药,或在最后一天单次注射(5 和 10mg/kg)给药。两种治疗形式的尼莫地平均可预防自发吗啡戒断后的记忆障碍。在戒断期间,皮质酮浓度在小鼠的大脑和血液中增加,而尼莫地平预处理可防止大脑和血液皮质酮浓度的增加。结果表明,阻断 L 型钙通道可改善吗啡戒断引起的记忆缺陷。这表明在急性戒断阶段给予某种治疗,如尼莫地平,可以预防戒断期间的记忆缺陷。