ROCK inhibition produces anxiety-related behaviors in mice

Rationale The 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. Objective To 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. Results In 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. Conclusion Our 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.