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

• Published in: Behavioural brain research 2014-11, Vol.274, p.235-242
• Main Authors: KISHIKAWA, Yuki, KAWAHARA, Yukie, YAMADA, Makiko, KANEKO, Fumi, KAWAHARA, Hiroshi, NISHI, Akinori
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Attention Deficit Disorder with Hyperactivity - complications; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit disorders. Hyperactivity; Biological and medical sciences; Central Nervous System Stimulants - therapeutic use; Child clinical studies; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Maze Learning - drug effects; Medical sciences; Methylphenidate - therapeutic use; Motor Activity - drug effects; Motor Activity - genetics; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Inbred SHR; Rats, Wistar
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2014.08.026

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.