title: Atomoxetine reduces hyperactive/impulsive behaviours in neurokinin-1 receptor 'knockout' mice.
abstract: BACKGROUND
  Mice with functional ablation of the neurokinin-1 receptor gene (NK1R(-/-)) display behavioural abnormalities which resemble the hyperactivity, inattention and impulsivity seen in Attention Deficit Hyperactivity Disorder (ADHD). Here, we investigated whether the established ADHD treatment, atomoxetine, alleviates these abnormalities when tested in the light/dark exploration box (LDEB) and 5-Choice Serial Reaction-Time Task (5-CSRTT).
  
  
  METHODS
  Separate cohorts of mice were tested in the 5-CSRTT and LDEB after treatment with no injection, vehicle or atomoxetine (5-CSRTT: 0.3, 3 or 10mg/kg; LDEB: 1, 3 or 10mg/kg).
  
  
  RESULTS
  Atomoxetine reduced the hyperactivity displayed by NK1R(-/-) mice in the LDEB at a dose (3mg/kg) which did not affect the locomotor activity of wildtypes. Atomoxetine (10mg/kg) also reduced impulsivity in NK1R(-/-) mice, but not wildtypes, in the 5-CSRTT. No dose of drug affected attention in either genotype.
  
  
  CONCLUSIONS
  This evidence that atomoxetine reduces hyperactive/impulsive behaviours in NK1R(-/-) mice consolidates the validity of using NK1R(-/-) mice in research of the aetiology and treatment of ADHD.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St, London WC1E 6BT, UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Pillidge
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St, London WC1E 6BT, UK.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Porter
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St, London WC1E 6BT, UK.
authors.forename: Temis
authors.initials: T
authors.lastname: Vasili
authors.affiliation: RenaSci Ltd, BioCity, Pennyfoot Street, Nottingham, NG1 1GF, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Heal
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St, London WC1E 6BT, UK. Electronic address: c.stanford@ucl.ac.uk.
authors.forename: S Clare
authors.initials: SC
authors.lastname: Stanford
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D006948:Hyperkinesis / Q000188:drug therapy* / Q000378:metabolism*; D007175:Impulsive Behavior / Q000187:drug effects*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011437:Propylamines / Q000494:pharmacology / Q000627:therapeutic use*; D018040:Receptors, Neurokinin-1 / Q000172:deficiency*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D018040:Receptors, Neurokinin-1; D000069445:Atomoxetine Hydrochloride
keywords: 5-Choice Serial Reaction-Time Task; Atomoxetine; Attention Deficit Hyperactivity Disorder; Hyperactivity; Impulsivity; NK1R(−/−) ‘knockout’ mouse