title: Differences in the performance of NK1R-/- ('knockout') and wildtype mice in the 5‑Choice Continuous Performance Test.
abstract: Mice lacking functional NK1 (substance P-preferring) receptors typically display excessive inattentiveness (omission errors) and impulsivity (premature responses) when compared with wildtypes in the 5-Choice Serial Reaction-Time Test (5-CSRTT). These abnormal behaviours are analogous to those seen in humans suffering from Attention Deficit Hyperactivity Disorder (ADHD). Here we used the 5-Choice Continuous‑Performance Test (5C-CPT) to ascertain whether NK1R-/- mice also display excessive false alarms (an inappropriate response to a 'no-go' signal), which is another form of impulsive behaviour. NK1R-/- mice completed more trials than wildtypes, confirming their ability to learn and carry out the task. At the start of Stage 1 of training, but not subsequently, they also scored more premature responses than wildtypes. When the mice were tested for the first time, neither false alarms nor premature responses was higher in NK1R-/- mice than wildtypes but, as in the 5-CSRTT, the latter behaviour was strongly dependent on time of day. NK1R-/- mice expressed excessive perseveration during all stages of the 5C-CPT. This behaviour is thought to reflect compulsive checking, which is common in ADHD patients. These findings point to differences in the 5-CSRTT and 5C-CPT protocols that could be important for distinguishing why the cognitive performance and response control of NK1R-/- mice differs from their wildtypes. The results further lead to the prediction that ADHD patients with polymorphism of the TACR1 gene (the human equivalent of Nk1r) would express more perseveration, but not false alarms, in Continuous Performance Tests when compared with other groups of subjects.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, 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 Street, 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 Street, London WC1E 6BT, UK. Electronic address: c.stanford@ucl.ac.uk.
authors.forename: S Clare
authors.initials: SC
authors.lastname: Stanford
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Young
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity; D002755:Choice Behavior / Q000502:physiology*; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000502:physiology; D007175:Impulsive Behavior / Q000502:physiology; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000172:deficiency* / Q000235:genetics
chemical_list: D018040:Receptors, Neurokinin-1
keywords: 5-Choice Continuous-Performance Test; ADHD; False alarms; Impulsivity; Inattentiveness; Motor disinhibition; NK1 receptor; Perseveration; Premature responses