title: Enhancement of alcohol drinking in mice depends on alterations in RNA editing of serotonin 2C receptors.
abstract: Serotonin 2C receptors (5-HT(2C)R) are G-protein-coupled receptors with various actions, including involvement in drug addiction. 5-HT2CR undergoes mRNA editing, converting genomically encoded adenosine residues to inosines via adenosine deaminases acting on RNA (ADARs). Here we show that enhanced alcohol drinking behaviour in mice is associated with the degree of 5-HT(2C)R mRNA editing in the nucleus accumbens and dorsal raphe nuceus, brain regions important for reward and addiction. Following chronic alcohol vapour exposure, voluntary alcohol intake increased in C57BL/6J mice, but remained unchanged in C3H/HeJ and DBA/2J mice. 5-HT(2C)R mRNA editing frequency in both regions increased significantly in C57BL/6J mice, as did expressions of 5-HT(2C)R, ADAR1 and ADAR2, but not in other strains. Moreover, mice that exclusively express the unedited isoform (INI) of 5-HT(2C)R mRNA on a C57BL/6J background did not exhibit increased alcohol intake compared with wild-type mice. Our results indicate that alterations in 5-HT(2C)R mRNA editing underlie alcohol preference in mice.
authors.affiliation: Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8566, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Forensic Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8566, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8566, Japan.
authors.forename: Harutsugu
authors.initials: H
authors.lastname: Tatebe
authors.affiliation: Department of Microbiology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8566, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kita
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nishikura
authors.affiliation: Brain Science Institute, Graduate School of Brain Sciences, Tamagawa University, Machida, Tokyo 194-8610, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-8566, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015151:Immunoblotting; D007536:Isomerism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009714:Nucleus Accumbens / Q000378:metabolism*; D017393:RNA Editing; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D000243:Adenosine Deaminase