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Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine

A recurrent and devastating feature of addiction to a drug of abuse is its persistence, which is mediated by maladaptive long-term memories of the highly pleasurable experience initially associated with the consumption of the drug. We have recently found that members of the CPEB family of proteins (...

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Autores principales: Drisaldi, Bettina, Colnaghi, Luca, Levine, Amir, Huang, YanYou, Snyder, Anna M., Metzger, Daniel J., Theis, Martin, Kandel, Denise B., Kandel, Eric R., Fioriti, Luana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365288/
https://www.ncbi.nlm.nih.gov/pubmed/32742260
http://dx.doi.org/10.3389/fncel.2020.00207
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author Drisaldi, Bettina
Colnaghi, Luca
Levine, Amir
Huang, YanYou
Snyder, Anna M.
Metzger, Daniel J.
Theis, Martin
Kandel, Denise B.
Kandel, Eric R.
Fioriti, Luana
author_facet Drisaldi, Bettina
Colnaghi, Luca
Levine, Amir
Huang, YanYou
Snyder, Anna M.
Metzger, Daniel J.
Theis, Martin
Kandel, Denise B.
Kandel, Eric R.
Fioriti, Luana
author_sort Drisaldi, Bettina
collection PubMed
description A recurrent and devastating feature of addiction to a drug of abuse is its persistence, which is mediated by maladaptive long-term memories of the highly pleasurable experience initially associated with the consumption of the drug. We have recently found that members of the CPEB family of proteins (Cytoplasmic Polyadenylation Element-Binding Proteins) are involved in the maintenance of spatial memory. However, their possible role in the maintenance of memories that sustain addictive behavior has yet to be explored. Little is known about any of the mechanisms for maintaining memories for addictive behavior. To address the mechanisms whereby addictive behavior is maintained over time, we utilized a conditional transgenic mouse model expressing a dominant-negative version of CPEB1 that abolishes the activity in the forebrain of two of the four CPEB isoforms (CPEB1 and CPEB3). We found that, following cocaine administration, these dominant-negative (DN) CPEB mice showed a significant decrease, when compared to wild type (WT) mice, in both locomotor sensitizations and conditioned place preference (CPP), two indices of addictive behavior. Supporting these behavioral results, we also found a difference between WT and DN-CPEB1-3 mice in the cocaine-induced synaptic depression in the core of the Nucleus Accumbens (NAc). Finally, we found that (1) CPEB is reduced in transgenic mice following cocaine injections and that (2) FosB, known for its contribution to establishing the addictive phenotype, when its expression in the striatum is increased by drug administration, is a novel target of CPEBs molecules. Thus, our study highlights how CPEB1 and CPEB3 act on target mRNAs to build the neuroadaptative implicit memory responses that lead to the development of the cocaine addictive phenotypes in mammals.
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spelling pubmed-73652882020-07-31 Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine Drisaldi, Bettina Colnaghi, Luca Levine, Amir Huang, YanYou Snyder, Anna M. Metzger, Daniel J. Theis, Martin Kandel, Denise B. Kandel, Eric R. Fioriti, Luana Front Cell Neurosci Cellular Neuroscience A recurrent and devastating feature of addiction to a drug of abuse is its persistence, which is mediated by maladaptive long-term memories of the highly pleasurable experience initially associated with the consumption of the drug. We have recently found that members of the CPEB family of proteins (Cytoplasmic Polyadenylation Element-Binding Proteins) are involved in the maintenance of spatial memory. However, their possible role in the maintenance of memories that sustain addictive behavior has yet to be explored. Little is known about any of the mechanisms for maintaining memories for addictive behavior. To address the mechanisms whereby addictive behavior is maintained over time, we utilized a conditional transgenic mouse model expressing a dominant-negative version of CPEB1 that abolishes the activity in the forebrain of two of the four CPEB isoforms (CPEB1 and CPEB3). We found that, following cocaine administration, these dominant-negative (DN) CPEB mice showed a significant decrease, when compared to wild type (WT) mice, in both locomotor sensitizations and conditioned place preference (CPP), two indices of addictive behavior. Supporting these behavioral results, we also found a difference between WT and DN-CPEB1-3 mice in the cocaine-induced synaptic depression in the core of the Nucleus Accumbens (NAc). Finally, we found that (1) CPEB is reduced in transgenic mice following cocaine injections and that (2) FosB, known for its contribution to establishing the addictive phenotype, when its expression in the striatum is increased by drug administration, is a novel target of CPEBs molecules. Thus, our study highlights how CPEB1 and CPEB3 act on target mRNAs to build the neuroadaptative implicit memory responses that lead to the development of the cocaine addictive phenotypes in mammals. Frontiers Media S.A. 2020-07-09 /pmc/articles/PMC7365288/ /pubmed/32742260 http://dx.doi.org/10.3389/fncel.2020.00207 Text en Copyright © 2020 Drisaldi, Colnaghi, Levine, Huang, Snyder, Metzger, Theis, Kandel, Kandel and Fioriti. 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 Cellular Neuroscience
Drisaldi, Bettina
Colnaghi, Luca
Levine, Amir
Huang, YanYou
Snyder, Anna M.
Metzger, Daniel J.
Theis, Martin
Kandel, Denise B.
Kandel, Eric R.
Fioriti, Luana
Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine
title Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine
title_full Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine
title_fullStr Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine
title_full_unstemmed Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine
title_short Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine
title_sort cytoplasmic polyadenylation element binding proteins cpeb1 and cpeb3 regulate the translation of fosb and are required for maintaining addiction-like behaviors induced by cocaine
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365288/
https://www.ncbi.nlm.nih.gov/pubmed/32742260
http://dx.doi.org/10.3389/fncel.2020.00207
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