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 (...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.00207/full |
| _version_ | 1818235295158501376 |
|---|---|
| author | Bettina Drisaldi Luca Colnaghi Amir Levine YanYou Huang Anna M. Snyder Daniel J. Metzger Martin Theis Denise B. Kandel Denise B. Kandel Eric R. Kandel Eric R. Kandel Eric R. Kandel Eric R. Kandel Luana Fioriti Luana Fioriti Luana Fioriti |
| author_facet | Bettina Drisaldi Luca Colnaghi Amir Levine YanYou Huang Anna M. Snyder Daniel J. Metzger Martin Theis Denise B. Kandel Denise B. Kandel Eric R. Kandel Eric R. Kandel Eric R. Kandel Eric R. Kandel Luana Fioriti Luana Fioriti Luana Fioriti |
| author_sort | Bettina Drisaldi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T11:51:42Z |
| format | Article |
| id | doaj.art-eecf03f4d98040a38043da74d23a3a4a |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-12T11:51:42Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-eecf03f4d98040a38043da74d23a3a4a2022-12-22T00:25:18ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-07-011410.3389/fncel.2020.00207559001Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by CocaineBettina Drisaldi0Luca Colnaghi1Amir Levine2YanYou Huang3Anna M. Snyder4Daniel J. Metzger5Martin Theis6Denise B. Kandel7Denise B. Kandel8Eric R. Kandel9Eric R. Kandel10Eric R. Kandel11Eric R. Kandel12Luana Fioriti13Luana Fioriti14Luana Fioriti15Department of Neuroscience, Columbia University, New York, NY, United StatesDepartment of Neuroscience, Columbia University, New York, NY, United StatesDepartment of Neuroscience, Columbia University, New York, NY, United StatesDepartment of Neuroscience, Columbia University, New York, NY, United StatesDepartment of Neuroscience, Columbia University, New York, NY, United StatesDepartment of Neuroscience, Columbia University, New York, NY, United StatesDepartment of Neuroscience, Columbia University, New York, NY, United StatesMailman School of Public Health, Columbia University, New York, NY, United StatesDepartment of Epidemiology of Substance Abuse, New York State Psychiatric Institute, New York, NY, United StatesDepartment of Neuroscience, Columbia University, New York, NY, United StatesKavli Institute for Brain Science, Columbia University, New York, NY, United StatesMortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, United StatesHoward Hughes Medical Institute, Chevy Chase, MD, United StatesDepartment of Neuroscience, Columbia University, New York, NY, United StatesMortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, United StatesDulbecco Telethon Institute, Istituto di Ricerche Farmacologiche Mario Negri, Milan, ItalyA 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.https://www.frontiersin.org/article/10.3389/fncel.2020.00207/fullcytoplasmic polyadenylationprotein translationcocaineaddictive behaviordelta FosBFosB |
| spellingShingle | Bettina Drisaldi Luca Colnaghi Amir Levine YanYou Huang Anna M. Snyder Daniel J. Metzger Martin Theis Denise B. Kandel Denise B. Kandel Eric R. Kandel Eric R. Kandel Eric R. Kandel Eric R. Kandel Luana Fioriti Luana Fioriti Luana Fioriti Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine Frontiers in Cellular Neuroscience cytoplasmic polyadenylation protein translation cocaine addictive behavior delta FosB FosB |
| 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 | cytoplasmic polyadenylation protein translation cocaine addictive behavior delta FosB FosB |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.00207/full |
| work_keys_str_mv | AT bettinadrisaldi cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT lucacolnaghi cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT amirlevine cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT yanyouhuang cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT annamsnyder cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT danieljmetzger cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT martintheis cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT denisebkandel cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT denisebkandel cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT ericrkandel cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT ericrkandel cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT ericrkandel cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT ericrkandel cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT luanafioriti cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT luanafioriti cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine AT luanafioriti cytoplasmicpolyadenylationelementbindingproteinscpeb1andcpeb3regulatethetranslationoffosbandarerequiredformaintainingaddictionlikebehaviorsinducedbycocaine |