title: The behavioural response of mice lacking NK₁ receptors to guanfacine resembles its clinical profile in treatment of ADHD.
abstract: OBJECTIVE
  Mice with functional ablation of substance P-preferring neurokinin-1 receptors (NK1R-/- mice) display behavioural abnormalities resembling those in attention deficit hyperactivity disorder (ADHD). Here, we investigated whether the ADHD treatment, guanfacine, alleviated the hyperactivity and impulsivity/inattention displayed by NK1R-/- mice in the light/dark exploration box (LDEB) and 5-choice serial reaction-time task (5-CSRTT), respectively. Following reports of co-morbid anxiety in ADHD, we also investigated effects of guanfacine on anxiety-like behaviour displayed by NK1R-/- and wild-type (WT) mice in the elevated plus maze (EPM).
  
  
  METHODS
  Mice were treated with guanfacine (0.1, 0.3 or 1.0 mg·kg(-1), i.p.), vehicle or no injection and tested in the 5-CSRTT or the LDEB. Only the lowest dose of guanfacine was used in the EPM assays.
  
  
  RESULTS
  In the 5-CSRTT, a low dose of guanfacine (0.1 mg·kg(-1)) increased attention in NK1R-/- mice, but not in WT mice. This dose did not affect the total number of trials completed, latencies to respond or locomotor activity in the LDEB. Impulsivity was decreased by the high dose (1.0 mg·kg(-1)) of guanfacine, but this was evident in both genotypes and is likely to be secondary to a generalized blunting of behaviour. Although the NK1R-/- mice displayed marked anxiety-like behaviour, guanfacine did not affect the behaviour of either genotype in the EPM.
  
  
  CONCLUSIONS
  This evidence that guanfacine improves attention at a dose that did not affect arousal or emotionality supports our proposal that NK1R-/- mice express an attention deficit resembling that of ADHD patients.
authors: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors: Katharine
authors: K
authors: Pillidge
authors: Ashley J
authors: AJ
authors: Porter
authors: Julia A
authors: JA
authors: Dudley
authors: Yuan-Chen
authors: YC
authors: Tsai
authors: David J
authors: DJ
authors: Heal
authors: S Clare
authors: SC
authors: Stanford
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D016316:Guanfacine / Q000494:pharmacology*; D007175:Impulsive Behavior / Q000187:drug effects; D008297:Male; D018345:Mice, Knockout; D009042:Motivation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018040:Receptors, Neurokinin-1 / Q000172:deficiency / Q000235:genetics*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018040:Receptors, Neurokinin-1; D016316:Guanfacine