title: The spontaneously hypertensive rat/Izm (SHR/Izm) shows attention deficit/hyperactivity disorder-like behaviors but without impulsive behavior: therapeutic implications of low-dose methylphenidate.
abstract: The spontaneously hypertensive rat (SHR) has been used as a genetic animal model of attention deficit/hyperactivity disorder (ADHD). SHR/Izm is derived from stroke-resistant SHR as SHR/NIH and SHR/NCrl but from 22nd to 23rd generation descendants of the SHR/NIH ancestor and therefore may show different behavioral phenotypes compared to other SHR sub-strains. In this study, ADHD-like behaviors in SHR/Izm were evaluated compared to Wistar rats. SHR/Izm showed high locomotor activity in the habituation phase in a novel environment, although locomotor activity in the initial exploratory phase was low. In a behavioral test for attention, spontaneous alternation behavior in the Y-maze test was impaired in SHR/Izm. However, impulsive behavior in the elevated-plus maze test, which is designed to detect anxiety-related behavior but also reflects impulsivity for novelty seeking, was comparable to Wistar rats. Hyperactivity and inattention, detected as ADHD-like behaviors in SHR/Izm, were ameliorated with methylphenidate at a low dose (0.05mg/kg, i.p.). Therefore, SHR/Izm represents a unique animal model of ADHD without anxiety-related impulsive behavior.
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. Electronic address: a210gm019f@std.kurume-u.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kishikawa
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. Electronic address: yukikawa@med.kurume-u.ac.jp.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Kawahara
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan; Department of Psychiatry, Tokyo Women's Medical University, Kawada-Cho 8-1, Shinjuku-ku, Tokyo 168-8666, Japan. Electronic address: yamada.makiko@twmu.ac.jp.
authors.forename: Makiko
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. Electronic address: kaneko_fumi@kurume-u.ac.jp.
authors.forename: Fumi
authors.initials: F
authors.lastname: Kaneko
authors.affiliation: Department of Dental Anesthesiology, School of Dentistry, Tsurumi University, Tsurumi 2-1-3, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. Electronic address: kawahara-h@tsurumi-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawahara
authors.affiliation: Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. Electronic address: nishia@med.kurume-u.ac.jp.
authors.forename: Akinori
authors.initials: A
authors.lastname: Nishi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy* / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008774:Methylphenidate / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: Attention deficit/hyperactivity disorder (ADHD); Elevated plus maze test; Hyperactivity; Methylphenidate (MPH); Spontaneously hypertensive rat (SHR); Y-maze test