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Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration

Repeated self-administration of cocaine is associated with impairments in motivated behaviors as well as alterations in both dopamine (DA) release and neural signaling within the nucleus accumbens (NAc). These impairments are present even after several weeks of abstinence from drug taking, suggestin...

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Autor principal: Saddoris, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052666/
https://www.ncbi.nlm.nih.gov/pubmed/27752541
http://dx.doi.org/10.1523/ENEURO.0274-16.2016
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author Saddoris, Michael P.
author_facet Saddoris, Michael P.
author_sort Saddoris, Michael P.
collection PubMed
description Repeated self-administration of cocaine is associated with impairments in motivated behaviors as well as alterations in both dopamine (DA) release and neural signaling within the nucleus accumbens (NAc). These impairments are present even after several weeks of abstinence from drug taking, suggesting that the self-administration experience induces long-lasting neuroplastic alterations in the mesolimbic DA circuit. To understand these changes at the terminal level, rats were allowed to self-administer either cocaine intravenously (∼1 mg/kg per infusion) or water to a receptacle (control) in 2-h sessions over 14 days, followed by 30 days of enforced abstinence. Fast-scan cyclic voltammetry was used to record real-time DA release in either NAc core or shell after electrical stimulations of the ventral tegmental area (VTA) in freely-moving animals. In controls, the kinetics of DA release in the core and shell strikingly differed, with shell displaying slower release and reuptake rates than core. However, cocaine experience differentially altered these signaling patterns by NAc subregion. In the shell, cocaine rats showed less sensitivity to the dynamic range of applied stimulations than controls. In the core, by contrast, cocaine rats displayed robustly reduced peak DA release given the same stimulation, while also showing slower release and reuptake kinetics. The differential effects of cocaine self-administration on terminal function between core and shell is consistent with a region-specific functional reorganization of the mesolimbic DA system after repeated exposure and may provide an anatomical substrate for altered cognitive function after chronic drug-taking and addiction.
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spelling pubmed-50526662016-10-17 Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration Saddoris, Michael P. eNeuro New Research Repeated self-administration of cocaine is associated with impairments in motivated behaviors as well as alterations in both dopamine (DA) release and neural signaling within the nucleus accumbens (NAc). These impairments are present even after several weeks of abstinence from drug taking, suggesting that the self-administration experience induces long-lasting neuroplastic alterations in the mesolimbic DA circuit. To understand these changes at the terminal level, rats were allowed to self-administer either cocaine intravenously (∼1 mg/kg per infusion) or water to a receptacle (control) in 2-h sessions over 14 days, followed by 30 days of enforced abstinence. Fast-scan cyclic voltammetry was used to record real-time DA release in either NAc core or shell after electrical stimulations of the ventral tegmental area (VTA) in freely-moving animals. In controls, the kinetics of DA release in the core and shell strikingly differed, with shell displaying slower release and reuptake rates than core. However, cocaine experience differentially altered these signaling patterns by NAc subregion. In the shell, cocaine rats showed less sensitivity to the dynamic range of applied stimulations than controls. In the core, by contrast, cocaine rats displayed robustly reduced peak DA release given the same stimulation, while also showing slower release and reuptake kinetics. The differential effects of cocaine self-administration on terminal function between core and shell is consistent with a region-specific functional reorganization of the mesolimbic DA system after repeated exposure and may provide an anatomical substrate for altered cognitive function after chronic drug-taking and addiction. Society for Neuroscience 2016-10-06 /pmc/articles/PMC5052666/ /pubmed/27752541 http://dx.doi.org/10.1523/ENEURO.0274-16.2016 Text en Copyright © 2016 Saddoris http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Saddoris, Michael P.
Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration
title Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration
title_full Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration
title_fullStr Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration
title_full_unstemmed Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration
title_short Terminal Dopamine Release Kinetics in the Accumbens Core and Shell Are Distinctly Altered after Withdrawal from Cocaine Self-Administration
title_sort terminal dopamine release kinetics in the accumbens core and shell are distinctly altered after withdrawal from cocaine self-administration
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052666/
https://www.ncbi.nlm.nih.gov/pubmed/27752541
http://dx.doi.org/10.1523/ENEURO.0274-16.2016
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