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Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal

Cocaine use followed by withdrawal induces synaptic changes in nucleus accumbens (NAc), which are thought to underlie subsequent drug-seeking behaviors and relapse. Previous studies suggest that cocaine-induced synaptic changes depend on acid-sensing ion channels (ASICs). Here, we investigated poten...

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Autores principales: Gupta, Subhash C., Ghobbeh, Ali, Taugher-Hebl, Rebecca J., Fan, Rong, Hardie, Jason B., LaLumiere, Ryan T., Wemmie, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668291/
https://www.ncbi.nlm.nih.gov/pubmed/36383659
http://dx.doi.org/10.1126/sciadv.abq5058
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author Gupta, Subhash C.
Ghobbeh, Ali
Taugher-Hebl, Rebecca J.
Fan, Rong
Hardie, Jason B.
LaLumiere, Ryan T.
Wemmie, John A.
author_facet Gupta, Subhash C.
Ghobbeh, Ali
Taugher-Hebl, Rebecca J.
Fan, Rong
Hardie, Jason B.
LaLumiere, Ryan T.
Wemmie, John A.
author_sort Gupta, Subhash C.
collection PubMed
description Cocaine use followed by withdrawal induces synaptic changes in nucleus accumbens (NAc), which are thought to underlie subsequent drug-seeking behaviors and relapse. Previous studies suggest that cocaine-induced synaptic changes depend on acid-sensing ion channels (ASICs). Here, we investigated potential involvement of carbonic anhydrase 4 (CA4), an extracellular pH-buffering enzyme. We examined effects of CA4 in mice on ASIC-mediated synaptic transmission in medium spiny neurons (MSNs) in NAc, as well as on cocaine-induced synaptic changes and behavior. We found that CA4 is expressed in the NAc and present in synaptosomes. Disrupting CA4 either globally, or locally, increased ASIC-mediated synaptic currents in NAc MSNs and protected against cocaine withdrawal–induced changes in synapses and cocaine-seeking behavior. These findings raise the possibility that CA4 might be a previously unidentified therapeutic target for addiction and relapse.
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spelling pubmed-96682912022-11-29 Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal Gupta, Subhash C. Ghobbeh, Ali Taugher-Hebl, Rebecca J. Fan, Rong Hardie, Jason B. LaLumiere, Ryan T. Wemmie, John A. Sci Adv Neuroscience Cocaine use followed by withdrawal induces synaptic changes in nucleus accumbens (NAc), which are thought to underlie subsequent drug-seeking behaviors and relapse. Previous studies suggest that cocaine-induced synaptic changes depend on acid-sensing ion channels (ASICs). Here, we investigated potential involvement of carbonic anhydrase 4 (CA4), an extracellular pH-buffering enzyme. We examined effects of CA4 in mice on ASIC-mediated synaptic transmission in medium spiny neurons (MSNs) in NAc, as well as on cocaine-induced synaptic changes and behavior. We found that CA4 is expressed in the NAc and present in synaptosomes. Disrupting CA4 either globally, or locally, increased ASIC-mediated synaptic currents in NAc MSNs and protected against cocaine withdrawal–induced changes in synapses and cocaine-seeking behavior. These findings raise the possibility that CA4 might be a previously unidentified therapeutic target for addiction and relapse. American Association for the Advancement of Science 2022-11-16 /pmc/articles/PMC9668291/ /pubmed/36383659 http://dx.doi.org/10.1126/sciadv.abq5058 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Neuroscience
Gupta, Subhash C.
Ghobbeh, Ali
Taugher-Hebl, Rebecca J.
Fan, Rong
Hardie, Jason B.
LaLumiere, Ryan T.
Wemmie, John A.
Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
title Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
title_full Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
title_fullStr Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
title_full_unstemmed Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
title_short Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
title_sort carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668291/
https://www.ncbi.nlm.nih.gov/pubmed/36383659
http://dx.doi.org/10.1126/sciadv.abq5058
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