Behavioral and genetic evidence for a novel animal model of Attention-Deficit/Hyperactivity Disorder Predominantly Inatt
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Behavioral and genetic evidence for a novel animal model of Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Subtype T Sagvolden*1, T DasBanerjee2,3, Y Zhang-James2,3, FA Middleton2,3 and SV Faraone2,3 Address: 1Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway, 2Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY, USA and 3Department of Psychiatry, Upstate Medical University, Syracuse, NY, USA Email: T Sagvolden* - [email protected]; T DasBanerjee - [email protected]; Y Zhang-James - [email protected]; FA Middleton - [email protected]; SV Faraone - [email protected] * Corresponding author
Published: 1 December 2008 Behavioral and Brain Functions 2008, 4:56
doi:10.1186/1744-9081-4-56
Received: 31 July 2008 Accepted: 1 December 2008
This article is available from: http://www.behavioralandbrainfunctions.com/content/4/1/56 © 2008 Sagvolden et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: According to DSM-IV there are three subtypes of Attention-Deficit/Hyperactivity Disorder, namely: ADHD predominantly inattentive type (ADHD-PI), ADHD predominantly Hyperactive-Impulsive Type (ADHD-HI), and ADHD combined type (ADHD-C). These subtypes may represent distinct neurobehavioral disorders of childhood onset with separate etiologies. The diagnosis of ADHD is behaviorally based; therefore, investigations into its possible etiologies should be based in behavior. Animal models of ADHD demonstrate construct validity when they accurately reproduce elements of the etiology, biochemistry, symptoms, and treatment of the disorder. Spontaneously hypertensive rats (SHR) fulfill many of the validation criteria and compare well with clinical cases of ADHD-C. The present study describes a novel rat model of the predominantly inattentive subtype (ADHD-PI). Methods: ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. Several strains with varied genetic background were needed to determine what constitutes a normal comparison. Five groups of rats were used: SHR/NCrl spontaneously hypertensive and WKY/NCrl Wistar/Kyoto rats from Charles River; SD/NTac Sprague Dawley and WH/HanTac Wistar rats from Taconic Europe; and WKY/NHsd Wistar/ Kyoto rats from Harlan. DNA was analyzed to determine background differences in the strains by PCR genotyping of eight highly polymorphic microsatellite markers and 2625 single nucleotide polymorphisms (SNPs). Results: Compared to appropriate comparison strains (WKY/NHsd and SD/NTac rats), SHR/ NCrl showed ADHD-C-like behavior: striking overactivity and poor sustained attention. Compared to WKY/NHsd rats, WKY/NCrl rat
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