Institut National de la Santé et de la Recherche Médicale-UMR788, Le Kremlin-Bicêtre, France.
Psychopharmacology (Berl). 2012 Jun;221(3):493-509. doi: 10.1007/s00213-011-2597-5. Epub 2011 Dec 8.
Agomelatine is described as a novel and clinical effective antidepressant drug with melatonergic (MT(1)/MT(2)) agonist and 5-HT(2C) receptor antagonist properties. Previous studies suggest that modulation of neuronal plasticity and microtubule dynamics may be involved in the treatment of depression.
The present study investigated the effects of agomelatine on microtubular, synaptic and brain-derived neurotrophic factor (BDNF) proteins in selected rat brain regions.
Adult male rats received agomelatine (40 mg/kg i.p.) once a day for 22 days. The pro-cognitive effect of agomelatine was tested in the novel object recognition task and antidepressant activity in the forced swimming test. Microtubule dynamics markers, microtubule-associated protein type 2 (MAP-2), phosphorylated MAP-2, synaptic markers [synaptophysin, postsynaptic density-95 (PSD-95) and spinophilin] and BDNF were measured by Western blot in the hippocampus, amygdala and prefrontal cortex (PFC).
Agomelatine exerted pro-cognitive and antidepressant activity and induced molecular changes in the brain areas examined. Agomelatine enhanced microtubule dynamics in the hippocampus and to a higher magnitude in the amygdala. By contrast, in the PFC, a decrease in microtubule dynamics was observed. Spinophilin (dendritic spines marker) was decreased, and BDNF increased in the hippocampus. Synaptophysin (presynaptic) and spinophilin were increased in the PFC and amygdala, while PSD-95 (postsynaptic marker) was increased in the amygdala, consistent with the phenomena of synaptic remodelling.
Agomelatine modulates cytoskeletal microtubule dynamics and synaptic markers. This may play a role in its pharmacological behavioural effects and may result from the melatonergic agonist and 5-HT(2C) antagonist properties of the compound.
阿戈美拉汀被描述为一种新型的、具有临床疗效的抗抑郁药，具有褪黑素能（MT(1)/MT(2)）激动剂和 5-HT(2C)受体拮抗剂特性。先前的研究表明，神经元可塑性和微管动力学的调节可能与抑郁症的治疗有关。
本研究探讨了阿戈美拉汀对选定大鼠脑区微管、突触和脑源性神经营养因子（BDNF）蛋白的影响。
成年雄性大鼠每天腹腔注射阿戈美拉汀（40mg/kg），共 22 天。在新物体识别任务中测试阿戈美拉汀的认知增强作用，在强迫游泳试验中测试其抗抑郁作用。通过 Western blot 法测定海马体、杏仁核和前额叶皮质（PFC）中的微管动力学标志物微管相关蛋白 2（MAP-2）、磷酸化 MAP-2、突触标志物[突触小体相关蛋白、突触后密度蛋白-95（PSD-95）和棘突蛋白]和 BDNF。
阿戈美拉汀具有认知增强和抗抑郁作用，并在检测的脑区引起分子变化。阿戈美拉汀增强了海马体中的微管动力学，在杏仁核中的增强程度更高。相比之下，在 PFC 中，微管动力学下降。海马体中的棘突蛋白（树突棘标志物）减少，BDNF 增加。突触小体相关蛋白（突触前）和棘突蛋白在 PFC 和杏仁核中增加，而 PSD-95（突触后标志物）在杏仁核中增加，这与突触重塑现象一致。
阿戈美拉汀调节细胞骨架微管动力学和突触标志物。这可能与其药理学行为效应有关，可能是由于该化合物的褪黑素能激动剂和 5-HT(2C)拮抗剂特性所致。
