Cabergoline, a dopamine receptor agonist, has an antidepressant-like property and enhances brain-derived neurotrophic factor signaling
Cabergoline, a dopamine receptor agonist, has an antidepressant-like property and enhances brain-derived neurotrophic factor signaling
复制标题
DOI：
10.1007/s00213-010-1894-8
复制
发表时间：
2010-08-01
影响因子：
3.4
通讯作者：
Kunugi, Hiroshi
中科院分区：
文献类型：
--
作者：
Chiba, Shuichi;Numakawa, Tadahiro;Kunugi, Hiroshi
多巴胺激动剂与抑郁症的治疗有关。卡麦角林是一种对多巴胺D-2样受体具有高亲和力的麦角衍生物;然而，关于其抗抑郁样作用的临床前研究很少。采用强迫游泳（FST）、新奇抑制进食（NST）、旷场（OFT）和高架迷宫（EPT）试验检测卡麦角林对大鼠行为的影响。在单次处理范例中，在单次注射卡麦角林（s.c.，0-4 A μ mol/kg）。在重复治疗范例中，在每日卡麦角林注射（s.c.，0.5 A μ mol/kg），然后在最后一次注射后24 h取出海马。在第14天在单独的实验中进行NST。Western blotting用于分析脑源性神经营养因子（BDNF）的蛋白水平和细胞内信号分子的激活。单次注射卡麦角林显示FST中的不动性和OFT中0-10 min的移动距离减少，而4 μ mol/kg的花费时间和进入张开臂的时间增加。当卡麦角林重复给药时，FST中的不动性和NSF中的进食潜伏期显著减少，而OFT中的垂直运动增加。EPT组闭臂时间有缩短的趋势。长期给予卡麦角林后，BDNF的表达和细胞外信号调节激酶1的激活上调，卡麦角林具有抗抑郁和抗焦虑样作用，这可能是通过增强BDNF的细胞内信号传导介导的。
Dopamine agonists have been implicated in the treatment of depression. Cabergoline is an ergot derivative with a high affinity to dopamine D-2-like receptors; however, there have been few preclinical studies on its antidepressant-like effects.Behavioral effects of cabergoline were examined in rats using forced swimming (FST), novelty-suppressed feeding (NST), open field (OFT), and elevated-plus maze (EPT) tests. In a single treatment paradigm, behaviors of rats were analyzed 4 h after single injection of cabergoline (s.c., 0-4 A mu mol/kg). In a repeated-treatment paradigm, OFT, EPT, and FST were conducted on days 11, 12, and13-14, respectively, during daily cabergoline injections (s.c., 0.5 A mu mol/kg), and then hippocampus was removed 24 h after the last injection. NST was conducted in a separate experiment at day 14. Western blotting was used for the analysis of the protein levels of brain-derived neurotrophic factor (BDNF) and the activation of intracellular signaling molecules.Single injection of cabergoline demonstrated decreased immobility in FST and distance traveled during 0-10 min in OFT, while time spent and entry into open arms were increased at 4 A mu mol/kg. When cabergoline was repeatedly administered, immobility in FST and the latency of feeding in NSF were significantly reduced, while vertical movement was increased in OFT. The time in closed arms was tended to be decreased in EPT. Expression of BDNF and activation of extracellular signal-regulated kinase 1 were up-regulated after the chronic administration of cabergoline.Cabergoline exerts antidepressant- and anxiolytic-like effects, which may be mediated by potentiation of intracellular signaling of BDNF.