The spontaneously hypertensive rat/Izm (SHR/Izm) shows attention deficit/hyperactivity disorder-like behaviors but without impulsive behavior: therapeutic implications of low-dose methylphenidate

Yuki Kishikawa; Yukie Kawahara; Makiko Yamada; Fumi Kaneko; Hiroshi Kawahara; Akinori Nishi

doi:10.1016/j.bbr.2014.08.026

The spontaneously hypertensive rat/Izm (SHR/Izm) shows attention deficit/hyperactivity disorder-like behaviors but without impulsive behavior: therapeutic implications of low-dose methylphenidate

Behav Brain Res. 2014 Nov 1:274:235-42. doi: 10.1016/j.bbr.2014.08.026. Epub 2014 Aug 20.

Authors

Yuki Kishikawa¹, Yukie Kawahara², Makiko Yamada³, Fumi Kaneko⁴, Hiroshi Kawahara⁵, Akinori Nishi⁶

Affiliations

¹ Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. Electronic address: a210gm019f@std.kurume-u.ac.jp.
² Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. Electronic address: yukikawa@med.kurume-u.ac.jp.
³ 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.
⁴ Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. Electronic address: kaneko_fumi@kurume-u.ac.jp.
⁵ 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.
⁶ Department of Pharmacology, Kurume University School of Medicine, Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan. Electronic address: nishia@med.kurume-u.ac.jp.

PMID: 25151620
DOI: 10.1016/j.bbr.2014.08.026

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.

Keywords: Attention deficit/hyperactivity disorder (ADHD); Elevated plus maze test; Hyperactivity; Methylphenidate (MPH); Spontaneously hypertensive rat (SHR); Y-maze test.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Attention Deficit Disorder with Hyperactivity / complications
Attention Deficit Disorder with Hyperactivity / drug therapy*
Attention Deficit Disorder with Hyperactivity / genetics*
Central Nervous System Stimulants / therapeutic use*
Disease Models, Animal
Dose-Response Relationship, Drug
Male
Maze Learning / drug effects
Methylphenidate / therapeutic use*
Motor Activity / drug effects
Motor Activity / genetics
Rats
Rats, Inbred SHR
Rats, Wistar

Substances

Central Nervous System Stimulants
Methylphenidate