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

被引:56
作者
Conboy, Lisa [1 ]
Tanrikut, Cihan [1 ]
Zoladz, Phillip R. [2 ,5 ,6 ]
Campbell, Adam M. [7 ]
Park, Collin R. [2 ,5 ,6 ]
Gabriel, Cecilia [3 ]
Mocaer, Elisabeth [3 ]
Sandi, Carmen [1 ]
Diamond, David M. [2 ,4 ,5 ,6 ]
机构
[1] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lab Behav Genet, CH-1015 Lausanne, Switzerland
[2] VA Hosp, Tanipa, FL USA
[3] IRIS, Courbevoie, France
[4] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA
[5] Univ S Florida, Ctr Preclin & Clin Res PTSD, Tampa, FL 33620 USA
[6] Univ S Florida, Dept Mol Pharmacol & Physiol, Tampa, FL 33620 USA
[7] Univ S Florida, Dept Psychiat & Behav Med, Tampa, FL 33620 USA
基金
瑞士国家科学基金会;
关键词
Antidepressant; cell adhesion molecules; hippocampus; memory; stress; LONG-TERM POTENTIATION; ASPARTATE RECEPTOR ANTAGONIST; MAJOR DEPRESSIVE DISORDER; MELATONIN AGONIST; PSA-NCAM; CIRCADIAN SYSTEM; PREDATOR STRESS; NMDA RECEPTOR; SELECTIVE IMPAIRMENT; SYNAPTIC PLASTICITY;
D O I
10.1017/S1461145708009255
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:329 / 341
页数:13
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