ROCK inhibition produces anxiety-related behaviors in mice
ROCK inhibition produces anxiety-related behaviors in mice
复制标题
DOI：
10.1007/s00213-006-0466-4
复制
发表时间：
2006-07
影响因子：
3.4
通讯作者：
A. Saitoh;M. Yamada;M. Yamada;Shinya Kobayashi;Noritaka Hirose;K. Honda;J. Kamei
中科院分区：
文献类型：
--
作者：
A. Saitoh;M. Yamada;M. Yamada;Shinya Kobayashi;Noritaka Hirose;K. Honda;J. Kamei
Rho/Rho相关激酶（ROCK）在树突和轴突发育过程中调控树突和轴突形态的作用已引起广泛关注。然而，我们对Rho/ROCK通路在情绪行为中的作用知之甚少。目的探讨ROCK在情绪行为中的作用。我们研究了ROCK抑制剂Y27632如何影响小鼠在测量焦虑相关行为的三项行为测试中的表现。结果Y27632 （10 nmol，脑室内）可显著降低大鼠张开臂停留时间和进入张开臂的比例。在恐惧条件反射测试中，y27632处理的小鼠比盐水处理的小鼠更经常和更长时间地冻结。在孔板实验中，Y27632显著抑制了Y27632处理小鼠的头浸行为。另一方面，Y27632在y迷宫测试中没有产生自发改变的表现。这些结果表明，ROCK抑制增加了焦虑相关行为。结论ROCK通路参与了焦虑和恐惧相关行为的表达。此外，我们提出，如果Rho/ROCK通路在调节人类焦虑相关行为中发挥重要作用，它可能被证明是抗焦虑药的新系统。
RationaleThe role of Rho/Rho-associated kinase (ROCK) in regulating dendritic and axonal morphology during development has gained much attention. Very little is known, however, about the role of the Rho/ROCK pathway in emotional behavior.ObjectiveTo investigate the role of ROCK in emotional behaviors. We examined how the ROCK inhibitor Y27632 affects the performance of mice on three behavioral tests that measure anxiety-related behaviors.ResultsIn the elevated plus-maze test, Y27632 (10 nmol, intracerebroventricular) induced a significant decrease in the percentage of time spent in the open arms and in the percentage of entries into open arms. In the fear conditioning test, Y27632-treated mice froze significantly more often and longer than did saline-treated mice. In the hole-board test, Y27632 significantly suppressed head-dipping behavior in Y27632-treated mice than in saline-treated mice. On the other hand, Y27632 did not produce on spontaneous alteration performance in the Y-maze test. These results indicate that ROCK inhibition increased anxiety-related behaviors.ConclusionOur findings suggest that the ROCK pathway is involved in the expression of anxiety- and fear-related behaviors. Furthermore, we propose that if the Rho/ROCK pathway plays an important role in mediating anxiety-related behaviors in humans, it may prove to be a novel system for anxiolytics to target.