Ex Vivo And In Vivo Changes In Function Of The Serotonin 2c Receptor Due To Rna Editing

In vitro , RNA editing of the serotonin 2C receptor (5HT2CR) alters its signal transduction efficiency. Fully edited (VGV) 5HT2CR's show low constitutive and agonist‐stimulated activity, whereas non‐edited (INI) 5HT2CR's exhibit the converse pattern. To test whether 5HT2CR editing alters its function ex vivo , 125‐I DOI and 3‐H mesulergine autoradiography was performed on brain sections from mice solely expressing either the INI or VGV receptors. Similar to in vitro observations, VGV receptors exhibited decreased, whereas INI receptors exhibited increased high affinity G‐protein coupling relative to wild‐type (WT) receptors. In addition, relative to WT mice, INI expressing mice showed greater increases in plasma corticosterone following treatment with the 5HT2CR agonist, MK‐212. INI expressing mice did not show alterations in expression of glucocorticoid receptor, suggesting that changes in the stress circuit did not account for the differences in 5HT2CR agonist‐induced corticosterone release. These data show that editing of the 5HT2CR alters its function in vivo . Supported by: NIH T32‐ MH065215 (CEC) and R01‐MH34007 (ESB)