Journal article
Chronic G s Signaling in the Striatum Increases Anxiety-Related Behaviors Independent of Developmental Effects
The Journal of neuroscience, Vol.28(51), pp.13952-13956
12/17/2008
DOI: 10.1523/JNEUROSCI.4986-08.2008
PMID: 19091983
Abstract
Current research in the field of anxiety disorders is largely receptor-centric, leaving intracellular pathways largely unexplored. Galphas, 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 Galphas 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 Galphas (or Galphas*). The first line expressed Galphas* throughout postnatal forebrain neurons, while the second line of mice conditionally expressed Galphas* selectively in the striatum (Galphas*(str) mice). In the open field, both lines of mice showed a significant preference for the periphery suggesting that expression of Galphas* in the striatum alone was sufficient to produce an anxiogenic phenotype. In the light/dark box, Galphas*(str) mice exhibited longer latencies to enter the light and spent significantly less time in the lit compartment. Similarly, Galphas*(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 Galphas*(str) transgene during development, but not at testing, were normal on most measures. These observations show that chronic Galphas 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.
Details
- Title: Subtitle
- Chronic G s Signaling in the Striatum Increases Anxiety-Related Behaviors Independent of Developmental Effects
- Creators
- C FavillaT AbelM. P Kelly
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.28(51), pp.13952-13956
- DOI
- 10.1523/JNEUROSCI.4986-08.2008
- PMID
- 19091983
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 12/17/2008
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984071762502771
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