Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice
Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice
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DOI：
10.1016/j.neuropharm.2007.01.006
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发表时间：
2007-04-01
影响因子：
4.7
通讯作者：
Picciotto, Marina R.
中科院分区：
文献类型：
--
作者：
Mineur, Yann S.;Somenzi, Oli;Picciotto, Marina R.
烟草中的尼古丁被认为可以调节调节情绪的神经系统。此外，似乎可能是阻断而不是激活含β 2（β 2*）的烟碱乙酰胆碱受体（nAChR）可能导致抗抑郁样作用。我们在几项抗抑郁疗效试验中使用了金雀花碱（α 4/β 2*nAChRs的部分激动剂和α 3/β 4*nAChRs的完全激动剂）。此外，我们使用c-fos表达来确定金雀花碱的抗抑郁样作用的潜在神经生物学相关性。野靛碱在几种抗抑郁疗效的动物模型中具有抗抑郁样作用。此外，免疫组织化学分析表明，野靛碱可以减少c-fos免疫反应在基底外侧杏仁核的50%左右。这些数据表明金雀花碱在抗抑郁功效的啮齿动物模型中的作用类似于经典抗抑郁药。此外，野靛碱阻断α 4/β 2* nAChR的能力可能是其抗抑郁样性质的原因，这些可能是通过减少基底外侧杏仁核中的神经元活性介导的。这些研究还表明，α 4/β 2* nAChR的拮抗剂和部分激动剂将是开发新型抗抑郁药物的有趣靶点。(c)2007爱思唯尔有限公司保留所有权利。
The nicotine in tobacco is thought to modulate neuronal systems regulating mood. Moreover, it appears possible that blockade rather than activation of beta 2-containing (beta 2*) nicotinic acetylcholine receptors (nAChRs) may lead to antidepressant-like effects. We used cytisine, a partial agonist of alpha 4/beta 2*nAChRs and a full agonist at alpha 3/beta 4*nAChRs, in several tests of antidepressant efficacy. Further, we used c-fos expression to identify potential neurobiological correlates of the antidepressant-like effects of cytisine. Cytisine had anti depressant-like effects in several animal models of antidepressant efficacy. In addition, immunohistochemical analyses indicated that cytisine could reduce c-fos immunoreactivity in the basolateral amygdala by similar to 50%. These data show that cytisine acts like classical antidepressants in rodent models of antidepressant efficacy. In addition, cytisine's ability to block alpha 4/beta 2*nAChRs may be responsible for its antidepressant-like properties, and these may be mediated through a reduction of neuronal activity in the basolateral amygdala. These studies also suggest that both antagonists and partial agonists of alpha 4/beta 2*nAChRs would be interesting targets for the development of novel antidepressant drugs. (c) 2007 Elsevier Ltd. All rights reserved.