Antidepressant, anxiolytic and procognitive effects of rivastigmine and donepezil in the chronic mild stress model in rats.
Antidepressant, anxiolytic and procognitive effects of rivastigmine and donepezil in the chronic mild stress model in rats.
复制标题
DOI：
10.1007/s00213-016-4206-0
复制
发表时间：
2016-04
影响因子：
3.4
通讯作者：
Willner P
中科院分区：
文献类型：
--
作者：
Papp M;Gruca P;Lason-Tyburkiewicz M;Willner P
老年抑郁症的治疗因频繁并发认知障碍而变得复杂。抗痴呆药物对改善认知能力有一定功效，但关于此类药物对抑郁症状的影响的文献不一致。在这里，我们研究了抗痴呆药物在经过充分验证的抑郁症和认知障碍、慢性轻度应激（CMS）动物模型中是否具有抗抑郁样和促认知作用。大鼠接受 CMS 治疗总共 8 周。 2周后，每天对应激和非应激动物亚组进行治疗，持续5周，然后停药1周，使用媒介物、丙咪嗪（10 mg/kg）、卡巴拉汀（2 mg/kg）、多奈哌齐（0.3 mg/kg）或美金刚（5 mg/kg）。每周测试蔗糖摄入量，并在高架十字迷宫（第 7 周）和物体识别任务（第 7 周和第 8 周）中测试动物。 CMS 减少了蔗糖摄入量，在高架十字迷宫中产生焦虑作用，并损害了物体识别测试中的表现。丙咪嗪、卡巴拉汀和多奈哌齐在所有三项测试中均使表现正常化。美金刚具有抗焦虑和促认知作用，但不能逆转 CMS 引起的快感缺乏。事实上，所有三种抗痴呆药物都逆转了 CMS 引起的认知障碍，并且胆碱酯酶抑制剂（而非美金刚）在该模型中具有抗抑郁样作用，这表明不同的机制可能是 CMS 引起的快感缺失和认知障碍的基础。我们讨论这些发现的临床意义。
The treatment of depression in old age is complicated by frequent co-morbidity with cognitive impairment. Anti-dementia drugs have some efficacy to improve cognitive performance and there is an inconsistent literature regarding the effect of such drugs on depressive symptoms. Here, we have investigated whether anti-dementia drugs would have antidepressant-like and pro-cognitive effects in a well-validated animal model of depression and cognitive impairment, chronic mild stress (CMS). Rats were subjected to CMS for a total of 8 weeks. After 2 weeks, subgroups of stressed and non-stressed animals were treated daily, for 5 weeks followed by 1 week of drug withdrawal, with vehicle, imipramine (10 mg/kg), rivastigmine (2 mg/kg), donepezil (0.3 mg/kg) or memantine (5 mg/kg). Sucrose intake was tested weekly, and animals were also tested in the elevated plus maze (at week 7) and in an object recognition task (at weeks 7 and 8). CMS decreased sucrose intake, had an anxiogenic effect in the elevated plus maze, and impaired performance in the object recognition test. Imipramine, rivastigmine and donepezil normalized performance in all three tests. Memantine had anxiolytic and pro-cognitive effects, but did not reverse CMS-induced anhedonia. The fact that all three anti-dementia drugs reversed CMS-induced cognitive impairment and that cholinesterase inhibitors, but not memantine, have antidepressant-like effects in this model suggest that different mechanisms may underlie CMS-induced anhedonia and cognitive impairment. We discuss the clinical implications of these findings.