Intraindividual variability (IIV) in an animal model of ADHD - the Spontaneously Hypertensive Rat

Guy Ml Perry,Stephen V Faraone,Terje Sagvolden

doi:10.1186/1744-9081-6-56

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is characterized by numerous behaviors including inattention, hyperactivity and impulsiveness. ADHD-affected individuals also have high intra-individual variability (IIV) in reaction time. The genetic control of IIV is not well understood. The single study of the genetics of this phenomenon in humans detected only marginal associations between genotypes at two candidate genes for ADHD and variability in response time. The Spontaneously Hypertensive Rat (SHR/NCrl) is an animal model of ADHD, expressing high activity, inattention and impulsive behavior during operant and task tests. The SHR might be useful for identifying genes for variability, but it is not known whether it also expresses high IIV, as is symptomatic of ADHD. We therefore conducted an investigation of IIV in the SHR. We used 16 SHR/NCrl rats and 15 Wistar-Kyoto (WKY/Nico) controls applying a reinforcement schedule used in the validation of the SHR as an animal model of ADHD. We represented IIV as the average absolute deviation of individual behavior within the five 18-min segments of each experimental session from the average behavioral trait value within that session ('individual phenotypic dispersion', PDi). PDi for hyperactivity, impulsiveness and inattention in the SHR and WKY rats was analyzed using nonparametric ranking by experimental session. SHR/NCrl rats had higher PDi than WKY/Nico controls for impulsiveness and inattention. There was a significant upward trend for PDi over experimental segments within sessions for attention in SHR rats, but not in WKY. PDi for hyperactivity was correlated with PDi for impulsiveness and we therefore excluded observations associated with short IRTs (< 0.67s); dispersion in hyperactivity outside this interval was also significantly higher in SHR rats than in WKY rats. Some studies indicate the sharing of symptoms of hyperactivity and impulsiveness in SHR and ADHD-affected humans; high IIV in operant behavioral metrics suggests that the SHR may be useful in elucidating the genetic basis for IIV in humans.

Highlights

Attention-deficit/hyperactivity disorder (ADHD) is characterized by numerous behaviors including inattention, hyperactivity and impulsiveness
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common, highly heritable [1] and costly ($US 67B-116B) [1,2] disorder characterized by hyperactivity, impulsiveness and inattention
Since this is measured as variability in individual subjects within the task, it is termed intra-individual variability (IIV)

Summary

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is characterized by numerous behaviors including inattention, hyperactivity and impulsiveness. Many studies have shown that the Spontaneously Hypertensive Rat (SHR/NCrl) shows the full range of ADHD-like symptoms, including increased motor activity, impulsiveness (short inter-response time) and decreased attention [13,14,15,16,17]. SHR as well as ADHD-affected children show increased responding during a fixed-interval schedule of reinforcement as well as during extinction of learned behavior [15,16].

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