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Sustained MK-801 induced deficit in a novel probabilistic reversal learning task

Cognitive flexibility, the ability to adapt to unexpected changes, is critical for healthy environmental and social interactions, and thus to everyday functioning. In neuropsychiatric diseases, cognitive flexibility is often impaired and treatment options are lacking. Probabilistic reversal learning...

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Autores principales: Latuske, Patrick, von Heimendahl, Moritz, Deiana, Serena, Wotjak, Carsten T., du Hoffmann, Johann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614101/
https://www.ncbi.nlm.nih.gov/pubmed/36313373
http://dx.doi.org/10.3389/fphar.2022.898548
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author Latuske, Patrick
von Heimendahl, Moritz
Deiana, Serena
Wotjak, Carsten T.
du Hoffmann, Johann
author_facet Latuske, Patrick
von Heimendahl, Moritz
Deiana, Serena
Wotjak, Carsten T.
du Hoffmann, Johann
author_sort Latuske, Patrick
collection PubMed
description Cognitive flexibility, the ability to adapt to unexpected changes, is critical for healthy environmental and social interactions, and thus to everyday functioning. In neuropsychiatric diseases, cognitive flexibility is often impaired and treatment options are lacking. Probabilistic reversal learning (PRL) is commonly used to measure cognitive flexibility in rodents and humans. In PRL tasks, subjects must sample choice options and, from probabilistic feedback, find the current best choice which then changes without warning. However, in rodents, pharmacological models of human cognitive impairment tend to disrupt only the first (or few) of several contingency reversals, making quantitative assessment of behavioral effects difficult. To address this limitation, we developed a novel rat PRL where reversals occur at relatively long intervals in time that demonstrates increased sensitivity to the non-competitive NMDA receptor antagonist MK-801. Here, we quantitively compare behavior in time-based PRL with a widely used task where reversals occur based on choice behavior. In time-based PRL, MK-801 induced sustained reversal learning deficits both in time and across reversal blocks but, at the same dose, only transient weak effects in performance-based PRL. Moreover, time-based PRL yielded better estimates of behavior and reinforcement learning model parameters, which opens meaningful pharmacological windows to efficiently test and develop novel drugs preclinically with the goal of improving cognitive impairment in human patients.
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spelling pubmed-96141012022-10-29 Sustained MK-801 induced deficit in a novel probabilistic reversal learning task Latuske, Patrick von Heimendahl, Moritz Deiana, Serena Wotjak, Carsten T. du Hoffmann, Johann Front Pharmacol Pharmacology Cognitive flexibility, the ability to adapt to unexpected changes, is critical for healthy environmental and social interactions, and thus to everyday functioning. In neuropsychiatric diseases, cognitive flexibility is often impaired and treatment options are lacking. Probabilistic reversal learning (PRL) is commonly used to measure cognitive flexibility in rodents and humans. In PRL tasks, subjects must sample choice options and, from probabilistic feedback, find the current best choice which then changes without warning. However, in rodents, pharmacological models of human cognitive impairment tend to disrupt only the first (or few) of several contingency reversals, making quantitative assessment of behavioral effects difficult. To address this limitation, we developed a novel rat PRL where reversals occur at relatively long intervals in time that demonstrates increased sensitivity to the non-competitive NMDA receptor antagonist MK-801. Here, we quantitively compare behavior in time-based PRL with a widely used task where reversals occur based on choice behavior. In time-based PRL, MK-801 induced sustained reversal learning deficits both in time and across reversal blocks but, at the same dose, only transient weak effects in performance-based PRL. Moreover, time-based PRL yielded better estimates of behavior and reinforcement learning model parameters, which opens meaningful pharmacological windows to efficiently test and develop novel drugs preclinically with the goal of improving cognitive impairment in human patients. Frontiers Media S.A. 2022-10-14 /pmc/articles/PMC9614101/ /pubmed/36313373 http://dx.doi.org/10.3389/fphar.2022.898548 Text en Copyright © 2022 Latuske, von Heimendahl, Deiana, Wotjak and du Hoffmann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Latuske, Patrick
von Heimendahl, Moritz
Deiana, Serena
Wotjak, Carsten T.
du Hoffmann, Johann
Sustained MK-801 induced deficit in a novel probabilistic reversal learning task
title Sustained MK-801 induced deficit in a novel probabilistic reversal learning task
title_full Sustained MK-801 induced deficit in a novel probabilistic reversal learning task
title_fullStr Sustained MK-801 induced deficit in a novel probabilistic reversal learning task
title_full_unstemmed Sustained MK-801 induced deficit in a novel probabilistic reversal learning task
title_short Sustained MK-801 induced deficit in a novel probabilistic reversal learning task
title_sort sustained mk-801 induced deficit in a novel probabilistic reversal learning task
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614101/
https://www.ncbi.nlm.nih.gov/pubmed/36313373
http://dx.doi.org/10.3389/fphar.2022.898548
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