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Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior

Propensity to relapse, even following long periods of abstinence, is a key feature in substance use disorders. Relapse and relapse‐like behaviors are known to be induced, in part, by re‐exposure to drug‐associated cues. Yet, while many critical nodes in the neural circuitry contributing to relapse h...

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Autores principales: López, Alberto J., Jia, Yousheng, White, André O., Kwapis, Janine L., Espinoza, Monica, Hwang, Philip, Campbell, Rianne, Alaghband, Yasaman, Chitnis, Om, Matheos, Dina P., Lynch, Gary, Wood, Marcelo A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087687/
https://www.ncbi.nlm.nih.gov/pubmed/29430793
http://dx.doi.org/10.1111/adb.12605
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author López, Alberto J.
Jia, Yousheng
White, André O.
Kwapis, Janine L.
Espinoza, Monica
Hwang, Philip
Campbell, Rianne
Alaghband, Yasaman
Chitnis, Om
Matheos, Dina P.
Lynch, Gary
Wood, Marcelo A.
author_facet López, Alberto J.
Jia, Yousheng
White, André O.
Kwapis, Janine L.
Espinoza, Monica
Hwang, Philip
Campbell, Rianne
Alaghband, Yasaman
Chitnis, Om
Matheos, Dina P.
Lynch, Gary
Wood, Marcelo A.
author_sort López, Alberto J.
collection PubMed
description Propensity to relapse, even following long periods of abstinence, is a key feature in substance use disorders. Relapse and relapse‐like behaviors are known to be induced, in part, by re‐exposure to drug‐associated cues. Yet, while many critical nodes in the neural circuitry contributing to relapse have been identified and studied, a full description of the networks driving reinstatement of drug‐seeking behaviors is lacking. One area that may provide further insight to the mechanisms of relapse is the habenula complex, an epithalamic region composed of lateral and medial (MHb) substructures, each with unique cell and target populations. Although well conserved across vertebrate species, the functions of the MHb are not well understood. Recent research has demonstrated that the MHb regulates nicotine aversion and withdrawal. However, it remains undetermined whether MHb function is limited to nicotine and aversive stimuli or if MHb circuit regulates responses to other drugs of abuse. Advances in circuit‐level manipulations now allow for cell‐type and temporally specific manipulations during behavior, specifically in spatially restrictive brain regions, such as the MHb. In this study, we focus on the response of the MHb to reinstatement of cocaine‐associated behavior, demonstrating that cocaine‐primed reinstatement of conditioned place preference engages habenula circuitry. Using chemogenetics, we demonstrate that MHb activity is sufficient to induce reinstatement behavior. Together, these data identify the MHb as a key hub in the circuitry underlying reinstatement and may serve as a target for regulating relapse‐like behaviors.
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spelling pubmed-60876872019-05-21 Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior López, Alberto J. Jia, Yousheng White, André O. Kwapis, Janine L. Espinoza, Monica Hwang, Philip Campbell, Rianne Alaghband, Yasaman Chitnis, Om Matheos, Dina P. Lynch, Gary Wood, Marcelo A. Addict Biol Preclinical Studies Propensity to relapse, even following long periods of abstinence, is a key feature in substance use disorders. Relapse and relapse‐like behaviors are known to be induced, in part, by re‐exposure to drug‐associated cues. Yet, while many critical nodes in the neural circuitry contributing to relapse have been identified and studied, a full description of the networks driving reinstatement of drug‐seeking behaviors is lacking. One area that may provide further insight to the mechanisms of relapse is the habenula complex, an epithalamic region composed of lateral and medial (MHb) substructures, each with unique cell and target populations. Although well conserved across vertebrate species, the functions of the MHb are not well understood. Recent research has demonstrated that the MHb regulates nicotine aversion and withdrawal. However, it remains undetermined whether MHb function is limited to nicotine and aversive stimuli or if MHb circuit regulates responses to other drugs of abuse. Advances in circuit‐level manipulations now allow for cell‐type and temporally specific manipulations during behavior, specifically in spatially restrictive brain regions, such as the MHb. In this study, we focus on the response of the MHb to reinstatement of cocaine‐associated behavior, demonstrating that cocaine‐primed reinstatement of conditioned place preference engages habenula circuitry. Using chemogenetics, we demonstrate that MHb activity is sufficient to induce reinstatement behavior. Together, these data identify the MHb as a key hub in the circuitry underlying reinstatement and may serve as a target for regulating relapse‐like behaviors. John Wiley and Sons Inc. 2018-02-12 2019-05 /pmc/articles/PMC6087687/ /pubmed/29430793 http://dx.doi.org/10.1111/adb.12605 Text en © 2018 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Preclinical Studies
López, Alberto J.
Jia, Yousheng
White, André O.
Kwapis, Janine L.
Espinoza, Monica
Hwang, Philip
Campbell, Rianne
Alaghband, Yasaman
Chitnis, Om
Matheos, Dina P.
Lynch, Gary
Wood, Marcelo A.
Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior
title Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior
title_full Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior
title_fullStr Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior
title_full_unstemmed Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior
title_short Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior
title_sort medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior
topic Preclinical Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087687/
https://www.ncbi.nlm.nih.gov/pubmed/29430793
http://dx.doi.org/10.1111/adb.12605
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