title: A new mouse model of ADHD for medication development.
abstract: ADHD is a major societal problem with increasing incidence and a stagnant track record for treatment advances. A lack of appropriate animal models has partly contributed to the incremental advance of this field. Hence, our goal was to generate a novel mouse model that could be useful for ADHD medication development. We reasoned that hyperactivity is a core feature of ADHD that could easily be bred into a population, but to what extent other hallmark features of ADHD would appear as correlated responses was unknown. Hence, starting from a heterogeneous population, we applied within-family selection over 16 generations to produce a High-Active line, while simultaneously maintaining an unselected line to serve as the Control. We discovered that the High-Active line demonstrated motor impulsivity in two different versions of the Go/No-go test, which was ameliorated with a low dose of amphetamine, and further displayed hypoactivation of the prefrontal cortex and dysregulated cerebellar vermal activation as indexed by c-Fos immunohistochemical staining. We conclude that the High-Active line represents a valid model for the Hyperactive-Impulsive subtype of ADHD and therefore may be used in future studies to advance our understanding of the etiology of ADHD and screen novel compounds for its treatment.
authors.affiliation: The Neuroscience Program, University of Illinois, IL, USA.|The Beckman Institute for Advanced Science and Technology, University of Illinois, IL, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Majdak
authors.affiliation: Oak Ridge National Laboratory, University of Tennessee, Knoxville, TN, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Ossyra
authors.affiliation: College of Engineering, University of Tennessee, Knoxville, TN, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Ossyra
authors.affiliation: Department of Food Science and Technology, University of California, Davis, CA, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Cobert
authors.affiliation: College of Veterinary Medicine, University of Illinois, IL, USA.
authors.forename: Gabrielle C
authors.initials: GC
authors.lastname: Hofmann
authors.affiliation: The Beckman Institute for Advanced Science and Technology, University of Illinois, IL, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tse
authors.affiliation: The Beckman Institute for Advanced Science and Technology, University of Illinois, IL, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Panozzo
authors.affiliation: The Beckman Institute for Advanced Science and Technology, University of Illinois, IL, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Grogan
authors.affiliation: The Beckman Institute for Advanced Science and Technology, University of Illinois, IL, USA.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Sorokina
authors.affiliation: The Neuroscience Program, University of Illinois, IL, USA.|The Beckman Institute for Advanced Science and Technology, University of Illinois, IL, USA.|Department of Psychology, University of Illinois, IL, USA.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Rhodes
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology*; D002531:Cerebellum / Q000503:physiopathology; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D007150:Immunohistochemistry; D007175:Impulsive Behavior; D008297:Male; D018782:Maze Learning; D051379:Mice; D010641:Phenotype; D017397:Prefrontal Cortex / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos