ROCK inhibition produces anxiety-related behaviors in mice.
BACKGROUND
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.


CONCLUSIONS
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.
Saitoh
Akiyoshi
A
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, 142-8501, Japan.
Yamada
Mitsuhiko
M
Yamada
Misa
M
Kobayashi
Shinya
S
Hirose
Noritaka
N
Honda
Kazuo
K
Kamei
Junzo
J
D000577:Amides / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects; D019416:Head Movements / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology*; D012149:Restraint, Physical; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases