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5‐HT 2C receptor RNA editing in the amygdala of inbred mouse strains
Author(s) -
Hackler Elizabeth Ann,
Airey David C.,
Shan Caitlin C.,
Sodhi Monsheel S.,
SandersBush Elaine
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a249-d
Subject(s) - rna editing , amygdala , 5 ht2c receptor , receptor , anxiogenic , rna , gene isoform , anxiety , biology , neuroscience , psychology , serotonin , genetics , 5 ht receptor , gene , psychiatry , anxiolytic
The amygdala is a brain region integral to anxiety, fear, and related psychiatric disorders. Activation of G‐protein coupled 5‐hydroxytryptamine‐2C (5‐HT 2C ) receptors within the amygdala is anxiogenic. Post‐transcriptional RNA editing of 5‐HT 2C receptors predicts an array of 24 receptor isoforms, some of which are characterized by reduced constitutive activity and potency to initiate intracellular signaling. We hypothesized that inbred mouse strains known to differ in anxiety and fear should also differ in basal RNA editing profiles of the 5‐HT 2C receptor. Here we describe the RNA editing profiles from amygdala of two strains (BALB/cJ and DBA/2J) known to be more anxious than a third (C57BL/6J). We confirmed the strain anxiety differences and discovered that BALB/cJ and DBA/2J are each characterized by a higher functioning RNA editing profile than C57BL/6J. BALB/cJ and DBA/2J exhibit a roughly 2‐fold reduction in C site editing, and a corresponding 2‐fold reduction in the edited, functionally deficient VSV isoform. C57BL/6J is characterized by a relative decrease in the unedited, highly functional INI isoform. We further discovered that serotonin turnover is reduced in BALB/cJ and DBA/2J, consistent with emerging evidence that synaptic serotonin levels regulate RNA editing. We conclude that RNA editing is a potential correlate of amygdalar functions, including anxiety and fear. Future experiments will explore how pharmacological manipulations of 5‐HT 2C receptor RNA editing influence anxiety‐like behavior. Support Contributed By: T32 GM07628 and R01 MH34007