title: Pay attention to impulsivity: modelling low attentive and high impulsive subtypes of adult ADHD in the 5-choice continuous performance task (5C-CPT) in female rats.
abstract: Varying levels of attention and impulsivity deficits are core features of the three subtypes of adult attention deficit-hyperactivity disorder (ADHD). To date, little is known about the neurobiological correlates of these subtypes. Development of a translational animal model is essential to improve our understanding and improve therapeutic strategies. The 5-choice continuous performance task (5C-CPT) in rats can be used to examine different forms of attention and impulsivity. Adult rats were trained to pre-set 5C-CPT criterion and subsequently separated into subgroups according to baseline levels of sustained attention, vigilance, premature responding and response disinhibition in the 5C-CPT. The behavioural subgroups were selected to represent the different subtypes of adult ADHD. Consequently, effects of the clinically used pharmacotherapies (methylphenidate and atomoxetine) were assessed in the different subgroups. Four subgroups were identified: low-attentive (LA), high-attentive (HA), high-impulsive (HI) and low-impulsive (LI). Methylphenidate and atomoxetine produced differential effects in the subgroups. Methylphenidate increased sustained attention and vigilance in LA animals, and reduced premature responding in HI animals. Atomoxetine also improved sustained attention and vigilance in LA animals, and reduced response disinhibition and premature responding in HI animals. This is the first study using adult rats to demonstrate the translational value of the 5C-CPT to select subgroups of rats, which may be used to model the subtypes observed in adult ADHD. Our findings suggest that this as an important paradigm to increase our understanding of the neurobiological underpinnings of adult ADHD-subtypes and their response to pharmacotherapy.
authors.affiliation: Manchester Pharmacy School, University of Manchester, Oxford Road, Manchester M13 9PT, UK. Electronic address: anneka.tomlinson@postgrad.manchester.ac.uk.
authors.forename: Anneka
authors.initials: A
authors.lastname: Tomlinson
authors.affiliation: Manchester Pharmacy School, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Grayson
authors.affiliation: Manchester Pharmacy School, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Marsh
authors.affiliation: Manchester Pharmacy School, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Harte
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093-0603, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Barnes
authors.affiliation: Manchester Pharmacy School, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Kay M
authors.initials: KM
authors.lastname: Marshall
authors.affiliation: Manchester Pharmacy School, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Neill
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D007175:Impulsive Behavior / Q000187:drug effects / Q000502:physiology*; D008774:Methylphenidate / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride
keywords: Animal model; Atomoxetine; Cognition; Dopamine; Methylphenidate; Noradrenaline