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Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks

BACKGROUND: The inability to inhibit reinforced responses is a defining feature of ADHD associated with impulsivity. The Spontaneously Hypertensive Rat (SHR) has been extolled as an animal model of ADHD, but there is no clear experimental evidence of inhibition deficits in SHR. Attempts to demonstra...

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Autores principales: Sanabria, Federico, Killeen, Peter R
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276225/
https://www.ncbi.nlm.nih.gov/pubmed/18261220
http://dx.doi.org/10.1186/1744-9081-4-7
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author Sanabria, Federico
Killeen, Peter R
author_facet Sanabria, Federico
Killeen, Peter R
author_sort Sanabria, Federico
collection PubMed
description BACKGROUND: The inability to inhibit reinforced responses is a defining feature of ADHD associated with impulsivity. The Spontaneously Hypertensive Rat (SHR) has been extolled as an animal model of ADHD, but there is no clear experimental evidence of inhibition deficits in SHR. Attempts to demonstrate these deficits may have suffered from methodological and analytical limitations. METHODS: We provide a rationale for using two complementary response-withholding tasks to doubly dissociate impulsivity from motivational and motor processes. In the lever-holding task (LHT), continual lever depression was required for a minimum interval. Under a differential reinforcement of low rates schedule (DRL), a minimum interval was required between lever presses. Both tasks were studied using SHR and two normotensive control strains, Wistar-Kyoto (WKY) and Long Evans (LE), over an overlapping range of intervals (1 – 5 s for LHT and 5 – 60 s for DRL). Lever-holding and DRL performance was characterized as the output of a mixture of two processes, timing and iterative random responding; we call this account of response inhibition the Temporal Regulation (TR) model. In the context of TR, impulsivity was defined as a bias toward premature termination of the timed intervals. RESULTS: The TR model provided an accurate description of LHT and DRL performance. On the basis of TR parameter estimates, SHRs were more impulsive than LE rats across tasks and target times. WKY rats produced substantially shorter timed responses in the lever-holding task than in DRL, suggesting a motivational or motor deficit. The precision of timing by SHR, as measured by the variance of their timed intervals, was excellent, flouting expectations from ADHD research. CONCLUSION: This research validates the TR model of response inhibition and supports SHR as an animal model of ADHD-related impulsivity. It indicates, however, that SHR's impulse-control deficit is not caused by imprecise timing. The use of ad hoc impulsivity metrics and of WKY as control strain for SHR impulsivity are called into question.
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spelling pubmed-22762252008-03-28 Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks Sanabria, Federico Killeen, Peter R Behav Brain Funct Research BACKGROUND: The inability to inhibit reinforced responses is a defining feature of ADHD associated with impulsivity. The Spontaneously Hypertensive Rat (SHR) has been extolled as an animal model of ADHD, but there is no clear experimental evidence of inhibition deficits in SHR. Attempts to demonstrate these deficits may have suffered from methodological and analytical limitations. METHODS: We provide a rationale for using two complementary response-withholding tasks to doubly dissociate impulsivity from motivational and motor processes. In the lever-holding task (LHT), continual lever depression was required for a minimum interval. Under a differential reinforcement of low rates schedule (DRL), a minimum interval was required between lever presses. Both tasks were studied using SHR and two normotensive control strains, Wistar-Kyoto (WKY) and Long Evans (LE), over an overlapping range of intervals (1 – 5 s for LHT and 5 – 60 s for DRL). Lever-holding and DRL performance was characterized as the output of a mixture of two processes, timing and iterative random responding; we call this account of response inhibition the Temporal Regulation (TR) model. In the context of TR, impulsivity was defined as a bias toward premature termination of the timed intervals. RESULTS: The TR model provided an accurate description of LHT and DRL performance. On the basis of TR parameter estimates, SHRs were more impulsive than LE rats across tasks and target times. WKY rats produced substantially shorter timed responses in the lever-holding task than in DRL, suggesting a motivational or motor deficit. The precision of timing by SHR, as measured by the variance of their timed intervals, was excellent, flouting expectations from ADHD research. CONCLUSION: This research validates the TR model of response inhibition and supports SHR as an animal model of ADHD-related impulsivity. It indicates, however, that SHR's impulse-control deficit is not caused by imprecise timing. The use of ad hoc impulsivity metrics and of WKY as control strain for SHR impulsivity are called into question. BioMed Central 2008-02-08 /pmc/articles/PMC2276225/ /pubmed/18261220 http://dx.doi.org/10.1186/1744-9081-4-7 Text en Copyright © 2008 Sanabria and Killeen; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Sanabria, Federico
Killeen, Peter R
Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks
title Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks
title_full Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks
title_fullStr Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks
title_full_unstemmed Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks
title_short Evidence for impulsivity in the Spontaneously Hypertensive Rat drawn from complementary response-withholding tasks
title_sort evidence for impulsivity in the spontaneously hypertensive rat drawn from complementary response-withholding tasks
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276225/
https://www.ncbi.nlm.nih.gov/pubmed/18261220
http://dx.doi.org/10.1186/1744-9081-4-7
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