ROCK inhibition produces anxiety-related behaviors in mice

Psychopharmacology (Berl). 2006 Sep;188(1):1-11. doi: 10.1007/s00213-006-0466-4. Epub 2006 Jul 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / adverse effects
  • Amides / pharmacology*
  • Animals
  • Anxiety / chemically induced
  • Anxiety / metabolism*
  • Behavior, Animal / drug effects*
  • Cognition / drug effects
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology*
  • Fear / drug effects
  • Head Movements / drug effects
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Memory, Short-Term / drug effects
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism*
  • Pyridines / adverse effects
  • Pyridines / pharmacology*
  • Restraint, Physical
  • rho-Associated Kinases

Substances

  • Amides
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Pyridines
  • Y 27632
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases