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Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair
Author(s) -
Aoki Miku,
Watanabe Yoshihisa,
Yoshimoto Kanji,
Tsujimura Atsushi,
Yamamoto Toshiro,
Kanamura Narisato,
Tanaka Masaki
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13233
Subject(s) - rna editing , nucleus accumbens , gene isoform , serotonin , desipramine , neuropeptide y receptor , serotonergic , medicine , endocrinology , striatum , rna , receptor , neuropeptide , neuroscience , biology , psychology , dopamine , antidepressant , biochemistry , gene , hippocampus
Serotonin 2C receptors (5‐ HT 2 C R s) are widely expressed in the central nervous system, and are associated with various neurological disorders. 5‐ HT 2 C R m RNA 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‐ HT 2 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 C57 BL /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 ( NA c), amygdala, and striatum. They also showed reduced expression of neuropeptide Y ( NPY ) m RNA in the NA c. In addition, by stereotactic injection of adeno‐associated virus encoding NPY into the NA c, we demonstrated that accumbal NPY overexpression relieved behavioural despair. Our results suggest that accumbal NPY expression may be regulated by 5‐ HT 2 C R RNA editing, and its impairment may be linked to mood disorders.