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Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats

Anorexia nervosa has among the highest mortality rates of any psychiatric disorder and is characterized by cognitive inflexibility that persists after weight recovery and contributes to the chronic nature of the condition. What remains unknown is whether cognitive inflexibility predisposes individua...

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Autores principales: Huang, Kaixin, Milton, Laura K, Dempsey, Harry, Power, Stephen J, Conn, Kyna-Anne, Andrews, Zane B, Foldi, Claire J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344425/
https://www.ncbi.nlm.nih.gov/pubmed/37387293
http://dx.doi.org/10.7554/eLife.84961
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author Huang, Kaixin
Milton, Laura K
Dempsey, Harry
Power, Stephen J
Conn, Kyna-Anne
Andrews, Zane B
Foldi, Claire J
author_facet Huang, Kaixin
Milton, Laura K
Dempsey, Harry
Power, Stephen J
Conn, Kyna-Anne
Andrews, Zane B
Foldi, Claire J
author_sort Huang, Kaixin
collection PubMed
description Anorexia nervosa has among the highest mortality rates of any psychiatric disorder and is characterized by cognitive inflexibility that persists after weight recovery and contributes to the chronic nature of the condition. What remains unknown is whether cognitive inflexibility predisposes individuals to anorexia nervosa, a question that is difficult to address in human studies. Our previous work using the most well-established animal model of anorexia nervosa, known as activity-based anorexia (ABA) identified a neurobiological link between cognitive inflexibility and susceptibility to pathological weight loss in female rats. However, testing flexible learning prior to exposure to ABA in the same animals has been thus far impossible due to the length of training required and the necessity of daily handling, which can itself influence the development of ABA. Here, we describe experiments that validate and optimize the first fully-automated and experimenter-free touchscreen cognitive testing system for rats and use this novel system to examine the reciprocal links between reversal learning (an assay of cognitive flexibility) and weight loss in the ABA model. First, we show substantially reduced testing time and increased throughput compared to conventional touchscreen testing methods because animals engage in test sessions at their own direction and can complete multiple sessions per day without experimenter involvement. We also show that, contrary to expectations, cognitive inflexibility measured by this reversal learning task does not predispose rats to pathological weight loss in ABA. Instead, rats that were predisposed to weight loss in ABA were more quickly able to learn this reversal task prior to ABA exposure. Intriguingly, we show reciprocal links between ABA exposure and cognitive flexibility, with ABA-exposed (but weight-recovered) rats performing much worse than ABA naïve rats on the reversal learning task, an impairment that did not occur to the same extent in rats exposed to food restriction conditions alone. On the other hand, animals that had been trained on reversal learning were better able to resist weight loss upon subsequent exposure to the ABA model. We also uncovered some stable behavioral differences between ABA susceptible versus resistant rats during touchscreen test sessions using machine learning tools that highlight possible predictors of anorectic phenotypes. These findings shed new light on the relationship between cognitive inflexibility and pathological weight loss and provide targets for future studies using the ABA model to investigate potential novel pharmacotherapies for anorexia nervosa.
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spelling pubmed-103444252023-07-14 Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats Huang, Kaixin Milton, Laura K Dempsey, Harry Power, Stephen J Conn, Kyna-Anne Andrews, Zane B Foldi, Claire J eLife Neuroscience Anorexia nervosa has among the highest mortality rates of any psychiatric disorder and is characterized by cognitive inflexibility that persists after weight recovery and contributes to the chronic nature of the condition. What remains unknown is whether cognitive inflexibility predisposes individuals to anorexia nervosa, a question that is difficult to address in human studies. Our previous work using the most well-established animal model of anorexia nervosa, known as activity-based anorexia (ABA) identified a neurobiological link between cognitive inflexibility and susceptibility to pathological weight loss in female rats. However, testing flexible learning prior to exposure to ABA in the same animals has been thus far impossible due to the length of training required and the necessity of daily handling, which can itself influence the development of ABA. Here, we describe experiments that validate and optimize the first fully-automated and experimenter-free touchscreen cognitive testing system for rats and use this novel system to examine the reciprocal links between reversal learning (an assay of cognitive flexibility) and weight loss in the ABA model. First, we show substantially reduced testing time and increased throughput compared to conventional touchscreen testing methods because animals engage in test sessions at their own direction and can complete multiple sessions per day without experimenter involvement. We also show that, contrary to expectations, cognitive inflexibility measured by this reversal learning task does not predispose rats to pathological weight loss in ABA. Instead, rats that were predisposed to weight loss in ABA were more quickly able to learn this reversal task prior to ABA exposure. Intriguingly, we show reciprocal links between ABA exposure and cognitive flexibility, with ABA-exposed (but weight-recovered) rats performing much worse than ABA naïve rats on the reversal learning task, an impairment that did not occur to the same extent in rats exposed to food restriction conditions alone. On the other hand, animals that had been trained on reversal learning were better able to resist weight loss upon subsequent exposure to the ABA model. We also uncovered some stable behavioral differences between ABA susceptible versus resistant rats during touchscreen test sessions using machine learning tools that highlight possible predictors of anorectic phenotypes. These findings shed new light on the relationship between cognitive inflexibility and pathological weight loss and provide targets for future studies using the ABA model to investigate potential novel pharmacotherapies for anorexia nervosa. eLife Sciences Publications, Ltd 2023-06-30 /pmc/articles/PMC10344425/ /pubmed/37387293 http://dx.doi.org/10.7554/eLife.84961 Text en © 2023, Huang, Milton et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Huang, Kaixin
Milton, Laura K
Dempsey, Harry
Power, Stephen J
Conn, Kyna-Anne
Andrews, Zane B
Foldi, Claire J
Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
title Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
title_full Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
title_fullStr Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
title_full_unstemmed Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
title_short Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
title_sort rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10344425/
https://www.ncbi.nlm.nih.gov/pubmed/37387293
http://dx.doi.org/10.7554/eLife.84961
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