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Updated: Aug 16, 2026

Elevated Plus Maze for Mice
Published on: December 22, 2008
Genetic alteration of anxiety and stress-like behavior in mice lacking CaMKIV
Fanny W F Shum1, Shanelle W Ko, Yong-Seok Lee
1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. fanny.shum@utoronto.ca
Abstract:
Calcium-calmodulin-dependent protein kinase IV (CaMKIV) phosphorylates the major transcription factor cyclic AMP-response element binding protein (CREB), which plays a role in emotional behavior. Here, CaMKIV knockout mice (CaMKIV(-/-)) were tested in a battery of stress and anxiety-related behavioral tests, to determine if CaMKIV plays a role in emotional behavior. CaMKIV(-/-) exhibited a decrease in anxiety-like behavior in both the elevated plus maze and dark-light emergence tests when compared to wild-type mice. Both the acoustic startle response and prepulse inhibition of startle were decreased with the deletion of CaMKIV. In addition, CaMKIV(-/-) mice displayed a lack of stress-induced analgesia following restraint or cold swim stress. Our results demonstrate a key role for CaMKIV in anxiety and stress-related behavior.
Insights
Calcium-calmodulin-dependent protein kinase IV (CaMKIV) impacts emotional behavior. CaMKIV knockout mice showed reduced anxiety and stress responses, indicating CaMKIV
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Molecular Biology
Background:
- Calcium-calmodulin-dependent protein kinase IV (CaMKIV) phosphorylates CREB, a transcription factor involved in emotional behavior.
- The precise role of CaMKIV in anxiety and stress-related behaviors remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of CaMKIV in anxiety and stress-related behaviors using a knockout mouse model.
- To determine the impact of CaMKIV deletion on emotional behavior.
Main Methods:
- CaMKIV knockout mice (CaMKIV(-/-)) and wild-type littermates were subjected to a battery of behavioral tests.
- Tests included the elevated plus maze, dark-light emergence test, acoustic startle response, prepulse inhibition of startle, and stress-induced analgesia following restraint or cold swim stress.
Main Results:
- CaMKIV(-/-) mice exhibited significantly reduced anxiety-like behavior in the elevated plus maze and dark-light emergence tests.
- Acoustic startle response and prepulse inhibition of startle were diminished in CaMKIV(-/-) mice.
- CaMKIV(-/-) mice did not display stress-induced analgesia after restraint or cold swim stress.
Conclusions:
- CaMKIV plays a critical role in regulating anxiety and stress-related behaviors.
- CaMKIV is essential for normal emotional responses to stressors.
- Targeting CaMKIV may offer therapeutic potential for anxiety and stress-related disorders.

