title: Enhanced alcohol-drinking behavior associated with active ghrelinergic and serotoninergic neurons in the lateral hypothalamus and amygdala.
abstract: Central ghrelin is required for the rewarding properties of drug abuse. We investigated whether alcohol affects ghrelinergic, dopaminergic, and serotoninergic neurons and growth hormone secretagogue receptor 1A (GHS-R1A) levels in the reward system of the brain. Alcohol-naïve C57BL/6J mice received 2g/kg ethanol (EtOH) intraperitoneally (i.p.). Plasma ghrelin levels decreased between 1 and 4h. We investigated the effects of EtOH administration on plasma ghrelin levels in two different animal models at 1, 3, and 10months of age. Plasma ghrelin levels decreased following the EtOH treatment in 1- and 3-month-old short-term (1-day) alcohol vapor-exposed (STA) mice. In contrast, EtOH administration increased plasma ghrelin levels in 1- and 3-month-old long-term (20-day) alcohol vapor-exposed (LTA) mice. In vivo ghrelin release in the lateral hypothalamus (LH) increased in STA and LTA mice after the i.p. administration of EtOH. EtOH increased in vivo dopamine (DA), but not serotonin (5-HT) release in the LH of STA mice, and increased in vivo DA and 5-HT release in the LH of LTA mice. GHS-R1A mRNA expression and GHS-R1A protein levels in the LH were increased in LTA mice. The number of GHS-R1A-immunoreactive cells was greater in the LH and amygdala of LTA mice. These results support the neurobiological correlation between the development of drinking behavior and activation of ghrelinergic and serotonergic neurons in the LH. The activation of ghrelinergic systems in the amygdala may also induce an increase in 5-HT release in the LH during long-term alcohol intake.
authors.affiliation: Department of Forensic Medicine, Hiroshima University, Hiroshima, Japan; Department of Food Science and Biotechnology, Hiroshima Institute of Technology, Hiroshima, Japan. Electronic address: k.yoshimoto.ud@it-hiroshima.ac.jp.
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
authors.affiliation: Department of Forensic Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Basic Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Anatomy and Neurobiology, Dokkyo University School of Medicine, Tochigi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Anatomy and Neurobiology, Dokkyo University School of Medicine, Tochigi, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ueda
authors.affiliation: Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Kaneyasu
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inden
authors.affiliation: Department of Physiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Marunaka
authors.affiliation: Department of Food Science and Biotechnology, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hattori
authors.affiliation: Department of Food Science and Biotechnology, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Department of Food Science and Biotechnology, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Tokaji
authors.affiliation: Department of Food Science and Biotechnology, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Ochi
mesh_terms: D000428:Alcohol Drinking; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D054439:Ghrelin / Q000097:blood / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054440:Receptors, Ghrelin / Q000032:analysis / Q000235:genetics / Q000502:physiology; D059326:Serotonergic Neurons / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism
chemical_list: D054439:Ghrelin; D054440:Receptors, Ghrelin; D012701:Serotonin; D004298:Dopamine
keywords: Alcohol-drinking behavior; Dopamine; Ghrelin; Lateral hypothalamus; Serotonin