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Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear

Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibi...

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Autores principales: Ma, Cassandra, Jean-Richard-dit-Bressel, Philip, Roughley, Stephanie, Vissel, Bryce, Balleine, Bernard W, Killcross, Simon, Bradfield, Laura A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152850/
https://www.ncbi.nlm.nih.gov/pubmed/34296108
http://dx.doi.org/10.1093/texcom/tgaa039
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author Ma, Cassandra
Jean-Richard-dit-Bressel, Philip
Roughley, Stephanie
Vissel, Bryce
Balleine, Bernard W
Killcross, Simon
Bradfield, Laura A
author_facet Ma, Cassandra
Jean-Richard-dit-Bressel, Philip
Roughley, Stephanie
Vissel, Bryce
Balleine, Bernard W
Killcross, Simon
Bradfield, Laura A
author_sort Ma, Cassandra
collection PubMed
description Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here, we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented rats from learning to avoid a lever that was punished with a stimulus that coterminated with footshock. Our second experiment demonstrated that retrieval of punishment learning is also somewhat mOFC-dependent, as lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent rats from reacquiring the ability to avoid a punished lever when it was learned prior to lesions being administered. In both experiments, Pavlovian fear conditioning to the stimulus was intact for all animals. Together, these results reveal that the mOFC regulates punishment learning and retrieval in a manner that is separate from any role in Pavlovian fear conditioning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.
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spelling pubmed-81528502021-07-21 Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear Ma, Cassandra Jean-Richard-dit-Bressel, Philip Roughley, Stephanie Vissel, Bryce Balleine, Bernard W Killcross, Simon Bradfield, Laura A Cereb Cortex Commun Original Article Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsive disorders and related behaviors. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here, we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented rats from learning to avoid a lever that was punished with a stimulus that coterminated with footshock. Our second experiment demonstrated that retrieval of punishment learning is also somewhat mOFC-dependent, as lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent rats from reacquiring the ability to avoid a punished lever when it was learned prior to lesions being administered. In both experiments, Pavlovian fear conditioning to the stimulus was intact for all animals. Together, these results reveal that the mOFC regulates punishment learning and retrieval in a manner that is separate from any role in Pavlovian fear conditioning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders. Oxford University Press 2020-07-30 /pmc/articles/PMC8152850/ /pubmed/34296108 http://dx.doi.org/10.1093/texcom/tgaa039 Text en © The Author(s) 2020. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Ma, Cassandra
Jean-Richard-dit-Bressel, Philip
Roughley, Stephanie
Vissel, Bryce
Balleine, Bernard W
Killcross, Simon
Bradfield, Laura A
Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear
title Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear
title_full Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear
title_fullStr Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear
title_full_unstemmed Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear
title_short Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear
title_sort medial orbitofrontal cortex regulates instrumental conditioned punishment, but not pavlovian conditioned fear
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152850/
https://www.ncbi.nlm.nih.gov/pubmed/34296108
http://dx.doi.org/10.1093/texcom/tgaa039
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