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Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine

Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release...

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Autores principales: Covey, Dan P., Juliano, Steven A., Garris, Paul A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643976/
https://www.ncbi.nlm.nih.gov/pubmed/23671560
http://dx.doi.org/10.1371/journal.pone.0060763
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author Covey, Dan P.
Juliano, Steven A.
Garris, Paul A.
author_facet Covey, Dan P.
Juliano, Steven A.
Garris, Paul A.
author_sort Covey, Dan P.
collection PubMed
description Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties.
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spelling pubmed-36439762013-05-13 Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine Covey, Dan P. Juliano, Steven A. Garris, Paul A. PLoS One Research Article Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties. Public Library of Science 2013-05-03 /pmc/articles/PMC3643976/ /pubmed/23671560 http://dx.doi.org/10.1371/journal.pone.0060763 Text en © 2013 Covey et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Covey, Dan P.
Juliano, Steven A.
Garris, Paul A.
Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine
title Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine
title_full Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine
title_fullStr Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine
title_full_unstemmed Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine
title_short Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine
title_sort amphetamine elicits opposing actions on readily releasable and reserve pools for dopamine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643976/
https://www.ncbi.nlm.nih.gov/pubmed/23671560
http://dx.doi.org/10.1371/journal.pone.0060763
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