Selective CRF2 receptor agonists ameliorate the anxiety- and depression-like state developed during chronic nicotine treatment and consequent acute withdrawal in mice
Selective CRF2 receptor agonists ameliorate the anxiety- and depression-like state developed during chronic nicotine treatment and consequent acute withdrawal in mice
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DOI：
10.1016/j.brainres.2016.09.044
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发表时间：
2016-12-01
期刊：
影响因子：
2.9
通讯作者：
Szabo, Gyula
中科院分区：
文献类型：
--
作者：
Bagosi, Zsolt;Palotai, Miklos;Szabo, Gyula
本研究的目的是探讨促肾上腺皮质激素释放因子（CRF）2受体的选择性激动剂尿皮质素2（UCN 2）和尿皮质素3（UCN 3）对急性尼古丁戒断引起的小鼠焦虑和抑郁样症状的影响。为此，将雄性CFLP小鼠暴露于重复腹膜内（IP）注射尼古丁或盐水溶液7天，急性戒断1天，然后单次脑室内（ICV）注射UCN 2、UCN 3或盐水溶液。30分钟后，在高架十字迷宫试验或强迫游泳试验中观察小鼠的焦虑和抑郁样行为。5分钟的测试后，反映下丘脑-垂体-肾上腺（HPA）轴的活性的血浆皮质酮浓度也通过化学荧光法测定。一半动物在第8天接受ICV治疗并进行评价，另一半在第9天进行评价。在第8天，尼古丁处理的小鼠表现出抗焦虑和抑郁的体征，但血浆皮质酮浓度没有显著升高。在第9天，尼古丁治疗的小鼠表现出焦虑和抑郁的迹象，血浆皮质酮水平显着增加。UCN 2或UCN 3的中枢给药改善了慢性尼古丁治疗后急性戒断期间出现的焦虑和抑郁样状态，包括HPA轴活动过度。目前的研究表明，选择性CRF 2受体激动剂可用作尼古丁成瘾的治疗。
The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1 day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution. After 30 min the mice were observed in an elevated plus-maze test or a forced swim test, for anxiety- and depression-like behavior. After 5 min of testing, the plasma corticosterone concentration reflecting the activity of the hypothalamic-pituitary adrenal (HPA) axis was also determined by a chemo-fluorescent method. Half of the animals were treated ICV and evaluated on the 8th day, the other half on the 9th day. On the 8th day, nicotine-treated mice presented signs of anxiolysis and depression, but no significant elevation of the plasma corticosterone concentration. On the 9th day, nicotine-treated mice exhibited signs of anxiety and depression and a significant increase of the plasma corticosterone levels. Central administration of UCN 2 or UCN 3 ameliorated the anxiety- and depression-like state including the hyperactivity of the HPA axis, developed during acute withdrawal following chronic nicotine treatment. The present study suggests that selective CRF2 receptor agonists could be used as a therapy in nicotine addiction.