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The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wildtype mice in the 5 Choice Serial Reaction Time Task

Weir, RK; Dudley, JA; Yan, TC; Grabowska, EM; Pena-Oliver, Y; Ripley, TL; Stephens, DN; ... Hunt, SP; + view all (2014) The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wildtype mice in the 5 Choice Serial Reaction Time Task. Journal of Psychopharmacology , 28 (3) pp. 270-281. 10.1177/0269881113495722. Green open access

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Abstract

Genetically-altered mice, lacking functional NK1 receptors (NK1R-/-), express abnormal behaviours that are prominent in Attention Deficit Hyperactivity Disorder: namely, inattentiveness and impulsivity (indicated by their greater %omissions and premature responses in the 5 Choice Serial Reaction Time Task: ‘5 CSRTT’) and locomotor hyperactivity. Here, we investigated how behaviour in the 5 CSRTT is affected by repeated testing and whether the abnormalities expressed by NK1R-/- mice are mimicked by treating wildtypes with an NK1R antagonist (L 733060 or RP 67580; 5 or 10 mg/kg). Repeated testing with a variable (VITI) or fixed, prolonged (LITI) intertrial interval reduced %omissions. Premature responses also declined, but only in NK1R /- mice in the VITI test. By contrast, perseveration increased in both genotypes. RP 67580 (10 mg/kg) increased the %omissions in both genotypes in the VITI, an action which cannot be attributed to NK1R antagonism. Neither drug affected perseveration. However, for premature responses, the profile of the response suggests that the low and high doses of RP 67580 (VITI) and L 733060 (LITI) have opposing effects on this behaviour. We infer that the effect of NK1R antagonists in the 5 CSRTT is confounded by animals’ test experience and non-specific drug effects at sites other than NK1R, possibly L type Ca2+v channels.

Type: Article
Title: The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wildtype mice in the 5 Choice Serial Reaction Time Task
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/0269881113495722
Publisher version: http://dx.doi.org/10.1177/0269881113495722
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page(http://www.uk.sagepub.com/aboutus/openaccess.htm).
Keywords: Attention deficit hyperactivity disorder, calcium channels, 5-Choice Serial Reaction-Time Task, Impulsivity, Inattentiveness, Locomotor hyperactivity, Mouse study, NK1 receptor, NK1 receptor antagonist, Perserveration, Substance P receptor
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1395805
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