title: A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice(1).
abstract: Mice lacking functional neurokinin-1 receptors (NK1R-/-) display abnormal behaviours seen in Attention Deficit Hyperactivity Disorder (hyperactivity, impulsivity and inattentiveness). These abnormalities were evident when comparing the behaviour of separate (inbred: 'Hom') wildtype and NK1R-/- mouse strains. Here, we investigated whether the inbreeding protocol could influence their phenotype by comparing the behaviour of these mice with that of wildtype (NK1R+/+) and NK1R-/- progeny of heterozygous parents ('Het', derived from the same inbred strains). First, we recorded the spontaneous motor activity of the two colonies/genotypes, over 7 days. This continuous monitoring also enabled us to investigate whether the diurnal rhythm in motor activity differs in the two colonies/genotypes. NK1R-/- mice from both colonies were hyperactive compared with their wildtypes and their diurnal rhythm was also disrupted. Next, we evaluated the performance of the four groups of mice in the 5-Choice Serial Reaction-Time Task (5-CSRTT). During training, NK1R-/- mice from both colonies expressed more impulsive and perseverative behaviour than their wildtypes. During testing, only NK1R-/- mice from the Hom colony were more impulsive than their wildtypes, but NK1R-/- mice from both colonies were more perseverative. There were no colony differences in inattentiveness. Moreover, a genotype difference in this measure depended on time of day. We conclude that the hyperactivity, perseveration and, possibly, inattentiveness of NK1R-/- mice is a direct consequence of a lack of functional NK1R. However, the greater impulsivity of NK1R-/- mice depended on an interaction between a functional deficit of NK1R and other (possibly environmental and/or epigenetic) factors.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology.
authors.forename: A J
authors.initials: AJ
authors.lastname: Porter
authors.forename: K
authors.initials: K
authors.lastname: Pillidge
authors.forename: Y C
authors.initials: YC
authors.lastname: Tsai
authors.forename: J A
authors.initials: JA
authors.lastname: Dudley
authors.forename: S P
authors.initials: SP
authors.lastname: Hunt
authors.forename: S N
authors.initials: SN
authors.lastname: Peirson
authors.forename: L A
authors.initials: LA
authors.lastname: Brown
authors.forename: S C
authors.initials: SC
authors.lastname: Stanford
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology*; D002755:Choice Behavior / Q000502:physiology*; D007175:Impulsive Behavior / Q000502:physiology*; D018345:Mice, Knockout; D010641:Phenotype; D011930:Reaction Time / Q000235:genetics; D018040:Receptors, Neurokinin-1 / Q000172:deficiency / Q000235:genetics*
chemical_list: D018040:Receptors, Neurokinin-1
keywords: 5-Choice Serial Reaction-Time Task; ADHD; NK1 receptor; TACR1 gene; attention; diurnal motor rhythm; epigenetics; hyperactivity; impulsivity; perseveration