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Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction

Despite decades of research, investigations into effective neural and pharmacological therapies for many drugs of abuse, such as cocaine, have produced no FDA-approved approaches. This difficulty derives from the complexity of substance use disorders, which encompass a variety of behavioral, psychol...

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Autores principales: Saddoris, Michael P., Siletti, Kayla A., Stansfield, Katherine J., Bercum, Maria Florencia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097772/
https://www.ncbi.nlm.nih.gov/pubmed/30115763
http://dx.doi.org/10.1101/lm.047019.117
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author Saddoris, Michael P.
Siletti, Kayla A.
Stansfield, Katherine J.
Bercum, Maria Florencia
author_facet Saddoris, Michael P.
Siletti, Kayla A.
Stansfield, Katherine J.
Bercum, Maria Florencia
author_sort Saddoris, Michael P.
collection PubMed
description Despite decades of research, investigations into effective neural and pharmacological therapies for many drugs of abuse, such as cocaine, have produced no FDA-approved approaches. This difficulty derives from the complexity of substance use disorders, which encompass a variety of behavioral, psychological, and neural circuit-based changes that occur as a result of repeated experience with the drug. Dopamine signaling has been demonstrated to play a key role in several aspects of drug abuse—from mediating its reinforcing properties and drug-seeking to triggering relapse—while also mediating a number of important aspects of normal (nondrug related) motivated behaviors and actions. Real-time recording methods such as in vivo voltammetry, electrophysiology, and calcium imaging demonstrate that the signaling properties of dopamine for motivationally relevant stimuli are highly dynamic and spatiotemporally circumscribed within afferent target regions. In this review, we identify the origins and functional consequences of heterogeneous dopamine release in the limbic system, and how these properties are persistently altered in the drug-experienced brain. We propose that these spatiotemporally parallel dopaminergic signals are simultaneously available to the animal, but that these circuits are impaired following prolonged drug experience by disrupting the location and content of dopamine signals in afferent target regions. These findings are discussed in the context of relapse and pathways to discovering new treatments for addiction disorders.
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spelling pubmed-60977722019-09-01 Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction Saddoris, Michael P. Siletti, Kayla A. Stansfield, Katherine J. Bercum, Maria Florencia Learn Mem Review Despite decades of research, investigations into effective neural and pharmacological therapies for many drugs of abuse, such as cocaine, have produced no FDA-approved approaches. This difficulty derives from the complexity of substance use disorders, which encompass a variety of behavioral, psychological, and neural circuit-based changes that occur as a result of repeated experience with the drug. Dopamine signaling has been demonstrated to play a key role in several aspects of drug abuse—from mediating its reinforcing properties and drug-seeking to triggering relapse—while also mediating a number of important aspects of normal (nondrug related) motivated behaviors and actions. Real-time recording methods such as in vivo voltammetry, electrophysiology, and calcium imaging demonstrate that the signaling properties of dopamine for motivationally relevant stimuli are highly dynamic and spatiotemporally circumscribed within afferent target regions. In this review, we identify the origins and functional consequences of heterogeneous dopamine release in the limbic system, and how these properties are persistently altered in the drug-experienced brain. We propose that these spatiotemporally parallel dopaminergic signals are simultaneously available to the animal, but that these circuits are impaired following prolonged drug experience by disrupting the location and content of dopamine signals in afferent target regions. These findings are discussed in the context of relapse and pathways to discovering new treatments for addiction disorders. Cold Spring Harbor Laboratory Press 2018-09 /pmc/articles/PMC6097772/ /pubmed/30115763 http://dx.doi.org/10.1101/lm.047019.117 Text en © 2018 Saddoris et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Review
Saddoris, Michael P.
Siletti, Kayla A.
Stansfield, Katherine J.
Bercum, Maria Florencia
Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction
title Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction
title_full Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction
title_fullStr Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction
title_full_unstemmed Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction
title_short Heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction
title_sort heterogeneous dopamine signals support distinct features of motivated actions: implications for learning and addiction
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097772/
https://www.ncbi.nlm.nih.gov/pubmed/30115763
http://dx.doi.org/10.1101/lm.047019.117
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