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Updated: May 25, 2026
Elevated Plus Maze for Mice
Published on: December 22, 2008
Regulator of calmodulin signaling knockout mice display anxiety-like behavior and motivational deficits
Maya M Davis1, Peter Olausson, Paul Greengard
1Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06508, USA.
Abstract:
Regulator of calmodulin (CaM) signaling (RCS), when phosphorylated by protein kinase A (PKA) on Ser55, binds to CaM and inhibits CaM-dependent signaling. RCS expression is high in the dorsal striatum, nucleus accumbens and amygdala, suggesting that the protein is involved in limbic-striatal function. To test this hypothesis, we examined RCS knockout (KO) mice in behavioral models dependent on these brain areas. Mice were tested for food-reinforced instrumental conditioning and responding under a progressive ratio (PR) schedule of reinforcement and in models of anxiety (elevated plus maze and open field). While RCS KO mice showed normal acquisition of a food-motivated instrumental response, they exhibited a lower breakpoint value when tested on responding under a PR schedule of reinforcement. RCS KO mice also displayed decreased exploration in both the open arms of an elevated plus maze and in the center region of an open field, suggesting an enhanced anxiety response. Biochemical studies revealed a reduction in the levels of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in the striatum of RCS KO mice. DARPP-32 is important in reward-mediated behavior, suggestive of a possible role for DARPP-32 in mediating some of the effects of RCS. Together these results implicate a novel PKA-regulated phosphoprotein, RCS, in the etiology of motivational deficits and anxiety.
Insights
Regulator of calmodulin signaling (RCS) knockout mice show reduced motivation and increased anxiety. This suggests RCS plays a role in anxiety and motivational deficits, potentially through its regulation of dopamine and cAMP-regulated phosphoprotein (DARPP-32).
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Science
Background:
- Regulator of calmodulin signaling (RCS) is a protein kinase A (PKA)-phosphorylated protein that inhibits calmodulin-dependent signaling.
- RCS is highly expressed in brain regions associated with limbic-striatal function, including the dorsal striatum, nucleus accumbens, and amygdala.
Purpose of the Study:
- To investigate the role of RCS in motivational behavior and anxiety using a knockout mouse model.
- To explore the potential involvement of dopamine and cAMP-regulated phosphoprotein (DARPP-32) in mediating RCS functions.
Main Methods:
- Behavioral testing of RCS knockout (KO) mice in food-reinforced instrumental conditioning and a progressive ratio (PR) schedule of reinforcement.
- Assessment of anxiety-like behaviors using the elevated plus maze and open field tests.
- Biochemical analysis of striatal DARPP-32 levels in RCS KO mice.
Main Results:
- RCS KO mice exhibited normal acquisition of food-motivated instrumental responses but showed a reduced breakpoint on a PR schedule, indicating motivational deficits.
- RCS KO mice displayed decreased exploration in the elevated plus maze and open field, suggesting enhanced anxiety.
- Striatal levels of DARPP-32 were reduced in RCS KO mice.
Conclusions:
- RCS plays a significant role in regulating motivational behavior and anxiety.
- The observed behavioral phenotypes in RCS KO mice may be partly mediated by alterations in DARPP-32 signaling.
- RCS is implicated as a novel PKA-regulated phosphoprotein involved in the etiology of motivational deficits and anxiety.
