Atomoxetine reduces hyperactive/impulsive behaviours in neurokinin-1 receptor 'knockout' mice

Pharmacol Biochem Behav. 2014 Dec;127:56-61. doi: 10.1016/j.pbb.2014.10.008. Epub 2014 Oct 24.


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.

Keywords: 5-Choice Serial Reaction-Time Task; Atomoxetine; Attention Deficit Hyperactivity Disorder; Hyperactivity; Impulsivity; NK1R(−/−) ‘knockout’ mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic Uptake Inhibitors / therapeutic use
  • Animals
  • Atomoxetine Hydrochloride
  • Hyperkinesis / drug therapy*
  • Hyperkinesis / metabolism*
  • Impulsive Behavior / drug effects*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Propylamines / pharmacology
  • Propylamines / therapeutic use*
  • Receptors, Neurokinin-1 / deficiency*


  • Adrenergic Uptake Inhibitors
  • Propylamines
  • Receptors, Neurokinin-1
  • Atomoxetine Hydrochloride