title: Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair.
abstract: Serotonin 2C receptors (5-HT2 C Rs) 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) or the fully edited VGV-isoform exhibit various phenotypes including metabolic abnormalities, aggressive behaviour, anxiety-like behaviour, and depression-like behaviour. Here, we examined the behavioural phenotype and molecular changes of INI mice on a C57BL/6J background. INI mice showed an enhanced behavioural despair in the forced swimming test, elevated sensitivity to the tricyclic antidepressant desipramine, and significantly decreased serotonin 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 demonstrated that accumbal NPY overexpression relieved behavioural 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.
authors.affiliation: Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Miku
authors.initials: M
authors.lastname: Aoki
authors.affiliation: Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Food Science and Biotechnology, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
authors.affiliation: Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tsujimura
authors.affiliation: Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Narisato
authors.initials: N
authors.lastname: Kanamura
authors.affiliation: Department of Basic Geriatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000374:Aggression; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000235:genetics / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D017393:RNA Editing; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D009478:Neuropeptide Y; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D003891:Desipramine
keywords: INI-isoform mouse; RNA editing; accumbal neuropeptide Y; behavioural despair; serotonin 2C receptor