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A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1

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...

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Autores principales: Porter, A J, Pillidge, K, Tsai, Y C, Dudley, J A, Hunt, S P, Peirson, S N, Brown, L A, Stanford, S C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415486/
https://www.ncbi.nlm.nih.gov/pubmed/25558794
http://dx.doi.org/10.1111/gbb.12195
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author Porter, A J
Pillidge, K
Tsai, Y C
Dudley, J A
Hunt, S P
Peirson, S N
Brown, L A
Stanford, S C
author_facet Porter, A J
Pillidge, K
Tsai, Y C
Dudley, J A
Hunt, S P
Peirson, S N
Brown, L A
Stanford, S C
author_sort Porter, A J
collection PubMed
description 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.
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spelling pubmed-44154862015-05-05 A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1 Porter, A J Pillidge, K Tsai, Y C Dudley, J A Hunt, S P Peirson, S N Brown, L A Stanford, S C Genes Brain Behav Original Articles 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. Blackwell Publishing Ltd 2015-02 2015-02-01 /pmc/articles/PMC4415486/ /pubmed/25558794 http://dx.doi.org/10.1111/gbb.12195 Text en © 2015 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Porter, A J
Pillidge, K
Tsai, Y C
Dudley, J A
Hunt, S P
Peirson, S N
Brown, L A
Stanford, S C
A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1
title A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1
title_full A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1
title_fullStr A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1
title_full_unstemmed A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1
title_short A lack of functional NK1 receptors explains most, but not all, abnormal behaviours of NK1R-/- mice1
title_sort lack of functional nk1 receptors explains most, but not all, abnormal behaviours of nk1r-/- mice1
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415486/
https://www.ncbi.nlm.nih.gov/pubmed/25558794
http://dx.doi.org/10.1111/gbb.12195
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