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Impulsive Action and Impulsive Choice Are Differentially Associated With Gene Expression Variations of the GABA(A) Receptor Alfa 1 Subunit and the CB(1) Receptor in the Lateral and Medial Orbitofrontal Cortices

The orbitofrontal cortex (OFC) is a key brain region for decision-making, action control and impulsivity. Quite notably, previous research has identified a double dissociation regarding the role of this cortical territory in impulsive choice. While medial orbitofrontal lesions increase preference fo...

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Autores principales: Ucha, Marcos, Roura-Martínez, David, Contreras, Ana, Pinto-Rivero, Sheyla, Orihuel, Javier, Ambrosio, Emilio, Higuera-Matas, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391359/
https://www.ncbi.nlm.nih.gov/pubmed/30842730
http://dx.doi.org/10.3389/fnbeh.2019.00022
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author Ucha, Marcos
Roura-Martínez, David
Contreras, Ana
Pinto-Rivero, Sheyla
Orihuel, Javier
Ambrosio, Emilio
Higuera-Matas, Alejandro
author_facet Ucha, Marcos
Roura-Martínez, David
Contreras, Ana
Pinto-Rivero, Sheyla
Orihuel, Javier
Ambrosio, Emilio
Higuera-Matas, Alejandro
author_sort Ucha, Marcos
collection PubMed
description The orbitofrontal cortex (OFC) is a key brain region for decision-making, action control and impulsivity. Quite notably, previous research has identified a double dissociation regarding the role of this cortical territory in impulsive choice. While medial orbitofrontal lesions increase preference for a large but delayed reward, lateral orbitofrontal lesions have the opposite effect. However, there are no data regarding this anatomical dissociation in impulsive action. The neurochemical basis of impulsivity is still being elucidated, however, in recent years a role for the endocannabinoids and the related glutamatergic and GABAergic neurotransmitter systems has been suggested. Here, we submitted male Wistar rats to a delay-discounting task (DDT) or a two-choice serial reaction time task (2-CSRTT) and classified them as high impulsive or low impulsive in either task using cluster analysis. We then examined the gene expression of several elements of the endocannabinoid system or different subunits of certain glutamatergic or GABAergic ionotropic receptors (AMPA, NMDA, or GABA(A)) in the lateral or medial divisions of their orbitofrontal cortices. Our results confirm, at the gene expression level, the dissociation in the participation of the medial, and lateral divisions of the orbitofrontal cortex in impulsivity. While in the 2-CSRTT (inhibitory control) we found that high impulsive animals exhibited lower gene expression levels of the α1 GABA(A) receptor subunit in the lateral OFC, no such differences were evident in the medial OFC. When we analyzed DDT performance, we found that high impulsive animals displayed lower levels of CB(1) gene expression in the medial but not in the lateral OFC. We propose that GABAergic dynamics in the lateral OFC might contribute to the inhibitory control mechanisms that are altered in impulsive behavior while endocannabinoid receptor gene transcription in the medial OFC may subserve the delay-discounting processes that participate in certain types of impulsiveness.
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spelling pubmed-63913592019-03-06 Impulsive Action and Impulsive Choice Are Differentially Associated With Gene Expression Variations of the GABA(A) Receptor Alfa 1 Subunit and the CB(1) Receptor in the Lateral and Medial Orbitofrontal Cortices Ucha, Marcos Roura-Martínez, David Contreras, Ana Pinto-Rivero, Sheyla Orihuel, Javier Ambrosio, Emilio Higuera-Matas, Alejandro Front Behav Neurosci Neuroscience The orbitofrontal cortex (OFC) is a key brain region for decision-making, action control and impulsivity. Quite notably, previous research has identified a double dissociation regarding the role of this cortical territory in impulsive choice. While medial orbitofrontal lesions increase preference for a large but delayed reward, lateral orbitofrontal lesions have the opposite effect. However, there are no data regarding this anatomical dissociation in impulsive action. The neurochemical basis of impulsivity is still being elucidated, however, in recent years a role for the endocannabinoids and the related glutamatergic and GABAergic neurotransmitter systems has been suggested. Here, we submitted male Wistar rats to a delay-discounting task (DDT) or a two-choice serial reaction time task (2-CSRTT) and classified them as high impulsive or low impulsive in either task using cluster analysis. We then examined the gene expression of several elements of the endocannabinoid system or different subunits of certain glutamatergic or GABAergic ionotropic receptors (AMPA, NMDA, or GABA(A)) in the lateral or medial divisions of their orbitofrontal cortices. Our results confirm, at the gene expression level, the dissociation in the participation of the medial, and lateral divisions of the orbitofrontal cortex in impulsivity. While in the 2-CSRTT (inhibitory control) we found that high impulsive animals exhibited lower gene expression levels of the α1 GABA(A) receptor subunit in the lateral OFC, no such differences were evident in the medial OFC. When we analyzed DDT performance, we found that high impulsive animals displayed lower levels of CB(1) gene expression in the medial but not in the lateral OFC. We propose that GABAergic dynamics in the lateral OFC might contribute to the inhibitory control mechanisms that are altered in impulsive behavior while endocannabinoid receptor gene transcription in the medial OFC may subserve the delay-discounting processes that participate in certain types of impulsiveness. Frontiers Media S.A. 2019-02-20 /pmc/articles/PMC6391359/ /pubmed/30842730 http://dx.doi.org/10.3389/fnbeh.2019.00022 Text en Copyright © 2019 Ucha, Roura-Martínez, Contreras, Pinto-Rivero, Orihuel, Ambrosio and Higuera-Matas. http://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 Neuroscience
Ucha, Marcos
Roura-Martínez, David
Contreras, Ana
Pinto-Rivero, Sheyla
Orihuel, Javier
Ambrosio, Emilio
Higuera-Matas, Alejandro
Impulsive Action and Impulsive Choice Are Differentially Associated With Gene Expression Variations of the GABA(A) Receptor Alfa 1 Subunit and the CB(1) Receptor in the Lateral and Medial Orbitofrontal Cortices
title Impulsive Action and Impulsive Choice Are Differentially Associated With Gene Expression Variations of the GABA(A) Receptor Alfa 1 Subunit and the CB(1) Receptor in the Lateral and Medial Orbitofrontal Cortices
title_full Impulsive Action and Impulsive Choice Are Differentially Associated With Gene Expression Variations of the GABA(A) Receptor Alfa 1 Subunit and the CB(1) Receptor in the Lateral and Medial Orbitofrontal Cortices
title_fullStr Impulsive Action and Impulsive Choice Are Differentially Associated With Gene Expression Variations of the GABA(A) Receptor Alfa 1 Subunit and the CB(1) Receptor in the Lateral and Medial Orbitofrontal Cortices
title_full_unstemmed Impulsive Action and Impulsive Choice Are Differentially Associated With Gene Expression Variations of the GABA(A) Receptor Alfa 1 Subunit and the CB(1) Receptor in the Lateral and Medial Orbitofrontal Cortices
title_short Impulsive Action and Impulsive Choice Are Differentially Associated With Gene Expression Variations of the GABA(A) Receptor Alfa 1 Subunit and the CB(1) Receptor in the Lateral and Medial Orbitofrontal Cortices
title_sort impulsive action and impulsive choice are differentially associated with gene expression variations of the gaba(a) receptor alfa 1 subunit and the cb(1) receptor in the lateral and medial orbitofrontal cortices
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391359/
https://www.ncbi.nlm.nih.gov/pubmed/30842730
http://dx.doi.org/10.3389/fnbeh.2019.00022
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