The Journal of Neuroscience, December 17, 2008, 28(51):13952-13956; doi:10.1523/JNEUROSCI.4986-08.2008
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Brief Communications
Chronic G
s Signaling in the Striatum Increases Anxiety-Related Behaviors Independent of Developmental Effects
Christopher Favilla,1
Ted Abel,1 and
Michele P. Kelly1,2
Departments of 1Biology and 2Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Correspondence should be addressed to Michele P. Kelly at her present address: Wyeth Research, Neuroscience/Room 1806, 865 Ridge Road, Monmouth, NJ 08852. Email: kellym22{at}wyeth.com
Current research in the field of anxiety disorders is largely receptor-centric, leaving intracellular pathways largely unexplored. G
s, the G-protein which stimulates adenylyl cyclase and L-type voltage-gated calcium channels, may be one intracellular molecule regulating anxiety-related behaviors as increased efficacy of Gs signaling has been noted in patient populations that suffer from anxiety. We report here anxiety-related behaviors in two lines of transgenic mice expressing a constitutively active isoform of Gs (or Gs*). The first line expressed Gs* throughout postnatal forebrain neurons, while the second line of mice conditionally expressed Gs* selectively in the striatum (Gs*str mice). In the open field, both lines of mice showed a significant preference for the periphery suggesting that expression of Gs* in the striatum alone was sufficient to produce an anxiogenic phenotype. In the light/dark box, Gs*str mice exhibited longer latencies to enter the light and spent significantly less time in the lit compartment. Similarly, Gs*str mice showed longer latencies to enter the open quadrants and spent less time in the open quadrants of the elevated zero maze. Interestingly, these anxiety-related phenotypes were largely unrelated to developmental effects as mice expressing the Gs*str transgene during development, but not at testing, were normal on most measures. These observations show that chronic Gs signaling in the striatum is sufficient to trigger anxiety-related behaviors largely independent of developmental effects and suggest the cAMP pathway or L-type voltage-gated calcium channels may be viable targets for future pharmacological intervention in the treatment of anxiety disorders.
Key words: GNAS; anxiety; panic disorder; striatum; cAMP; L-VGCC
Received Oct. 15, 2008;
accepted Nov. 11, 2008.
Correspondence should be addressed to Michele P. Kelly at her present address: Wyeth Research, Neuroscience/Room 1806, 865 Ridge Road, Monmouth, NJ 08852. Email: kellym22{at}wyeth.com
