The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats
The antidepressant agomelatine blocks the adverse effects of stress on memory and enables spatial learning to rapidly increase neural cell adhesion molecule (NCAM) expression in the hippocampus of rats
复制标题
DOI：
10.1017/s1461145708009255
复制
发表时间：
2009-04-01
影响因子：
4.8
通讯作者：
Diamond, David M.
中科院分区：
文献类型：
--
作者：
Conboy, Lisa;Tanrikut, Cihan;Diamond, David M.
阿戈美拉汀是一种具有临床疗效的新型抗抑郁药，作为褪黑激素受体激动剂和5-HT 2C受体拮抗剂发挥作用。由于应激是抑郁症发生的重要风险因素，因此我们试图确定阿戈美拉汀长期给药是否会阻断在径向臂水迷宫（RAWM）（一种视皮层依赖性空间记忆任务）中训练的大鼠中应激诱导的记忆障碍。此外，由于已知神经细胞粘附分子（NCAM）与记忆巩固和突触可塑性密切相关，因此我们评估了阿戈美拉汀对NCAM和多唾液酸化NCAM（PSA-NCAM）表达的影响，在有或无捕食者应激的空间记忆训练大鼠中进行。将成年雄性大鼠用阿戈美拉汀（10 mg/kg i. p.，每日一次，持续22天），然后进行一天的RAWM训练和记忆测试。大鼠进行了12次训练试验，然后将它们放在自己的笼子里（没有压力）或猫附近（捕食者压力）。30分钟后，老鼠接受记忆测试，随后立即进行大脑提取。我们发现：（1）阿戈美拉汀阻断捕食者应激诱导的空间记忆损伤;（2）阿戈美拉汀处理的应激和非应激大鼠在腹侧海马中表现出快速训练诱导的突触NCAM表达增加;（3）阿戈美拉汀处理阻断应激和非应激动物中水迷宫训练诱导的PSA-NCAM水平降低。这项工作提供了新的观察结果，表明阿戈美拉汀阻断了应激对大脑皮层依赖性记忆的不利影响，并激活了记忆储存的分子机制，以响应学习经历。
Agomelatine, a novel antidepressant with established clinical efficacy, acts as a melatonin receptor agonist and 5-HT2C receptor antagonist. As stress is a significant risk factor in the development of depression, we sought to determine if chronic agomelatine treatment would block the stress-induced impairment of memory in rats trained in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. Moreover, since neural cell adhesion molecule (NCAM) is known to be critically involved in memory consolidation and synaptic plasticity, we evaluated the effects of agomelatine on NCAM, and polysialylated NCAM (PSA-NCAM) expression in rats given spatial memory training with or without predator stress. Adult male rats were pre-treated with agomelatine (10 mg/kg i.p., daily for 22 d), followed by a single day of RAWM training and memory testing. Rats were given 12 training trials and then they were placed either in their home cages (no stress) or near a cat (predator stress). Thirty minutes later the rats were given a memory test trial followed immediately by brain extraction. We found that: (1) agomelatine blocked the predator stress-induced impairment of spatial memory; (2) agomelatine-treated stressed, as well as non-stressed, rats exhibited a rapid training-induced increase in the expression of synaptic NCAM in the ventral hippocampus; and (3) agomelatine treatment blocked the water-maze training-induced decrease in PSA-NCAM levels in both stressed and non-stressed animals. This work provides novel observations which indicate that agomelatine blocks the adverse effects of stress on hippocampus-dependent memory and activates molecular mechanisms of memory storage in response to a learning experience.