Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair.

Serotonin 2C receptors (5-HT2 C R) are widely expressed in the central nervous system, and are associated with various neurological disorders. 5-HT2 C R mRNA undergoes adenosine-to-inosine RNA editing at five sites within its coding sequence, resulting in expression of 24 different isoforms. Several edited isoforms show reduced activity, suggesting that RNA editing modulates serotonergic systems in the brain with causative relevance to neuropsychiatric disorders. Transgenic mice solely expressing the non-edited 5-HT2 C R INI-isoform (INI-mice) or the fully edited VGV-isoform (VGV-mice) exhibit various phenotypes including metabolic abnormalities, aggressive behavior, anxiety-like behavior, and depression-like behavior. Here, we examined the behavioral phenotype and molecular changes of INI-mice on a C57BL/6J background. INI-mice showed an enhanced behavioral despair in the forced swimming test, elevated sensitivity to the tricyclic antidepressant, desipramine, and significantly decreased 5-HT in the nucleus accumbens (NAc), amygdala, and striatum. They also showed reduced expression of neuropeptide Y (NPY) mRNA in the NAc. In addition, by stereotactic injection of adeno-associated virus encoding NPY into the NAc, we demonstrate that accumbal NPY overexpression relieves behavioral despair. Our results suggest that accumbal NPY expression may be regulated by 5-HT2 C R RNA editing, and its impairment may be linked to mood disorders. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved. Language: en