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Convergence of dopamine and glutamate signaling onto striatal ERK activation in response to drugs of abuse
Despite their distinct targets, all addictive drugs commonly abused by humans evoke increases in dopamine (DA) concentration within the striatum. The main DA Guanine nucleotide binding protein couple receptors (GPCRs) expressed by medium-sized spiny neurons of the striatum are the D1R and D2R, which...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884214/ https://www.ncbi.nlm.nih.gov/pubmed/24409148 http://dx.doi.org/10.3389/fphar.2013.00172 |
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author | Cahill, Emma Salery, Marine Vanhoutte, Peter Caboche, Jocelyne |
author_facet | Cahill, Emma Salery, Marine Vanhoutte, Peter Caboche, Jocelyne |
author_sort | Cahill, Emma |
collection | PubMed |
description | Despite their distinct targets, all addictive drugs commonly abused by humans evoke increases in dopamine (DA) concentration within the striatum. The main DA Guanine nucleotide binding protein couple receptors (GPCRs) expressed by medium-sized spiny neurons of the striatum are the D1R and D2R, which are positively and negatively coupled to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, respectively. These two DA GPCRs are largely segregated into distinct neuronal populations, where they are co-expressed with glutamate receptors in dendritic spines. Direct and indirect interactions between DA GPCRs and glutamate receptors are the molecular basis by which DA modulates glutamate transmission and controls striatal plasticity and behavior induced by drugs of abuse. A major downstream target of striatal D1R is the extracellular signal-regulated kinase (ERK) kinase pathway. ERK activation by drugs of abuse behaves as a key integrator of D1R and glutamate NMDAR signaling. Once activated, ERK can trigger chromatin remodeling and induce gene expression that permits long-term cellular alterations and drug-induced morphological and behavioral changes. Besides the classical cAMP/PKA pathway, downstream of D1R, recent evidence implicates a cAMP-independent crosstalk mechanism by which the D1R potentiates NMDAR-mediated calcium influx and ERK activation. The mounting evidence of reciprocal modulation of DA and glutamate receptors adds further intricacy to striatal synaptic signaling and is liable to prove relevant for addictive drug-induced signaling, plasticity, and behavior. Herein, we review the evidence that built our understanding of the consequences of this synergistic signaling for the actions of drugs of abuse. |
format | Online Article Text |
id | pubmed-3884214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-38842142014-01-09 Convergence of dopamine and glutamate signaling onto striatal ERK activation in response to drugs of abuse Cahill, Emma Salery, Marine Vanhoutte, Peter Caboche, Jocelyne Front Pharmacol Pharmacology Despite their distinct targets, all addictive drugs commonly abused by humans evoke increases in dopamine (DA) concentration within the striatum. The main DA Guanine nucleotide binding protein couple receptors (GPCRs) expressed by medium-sized spiny neurons of the striatum are the D1R and D2R, which are positively and negatively coupled to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, respectively. These two DA GPCRs are largely segregated into distinct neuronal populations, where they are co-expressed with glutamate receptors in dendritic spines. Direct and indirect interactions between DA GPCRs and glutamate receptors are the molecular basis by which DA modulates glutamate transmission and controls striatal plasticity and behavior induced by drugs of abuse. A major downstream target of striatal D1R is the extracellular signal-regulated kinase (ERK) kinase pathway. ERK activation by drugs of abuse behaves as a key integrator of D1R and glutamate NMDAR signaling. Once activated, ERK can trigger chromatin remodeling and induce gene expression that permits long-term cellular alterations and drug-induced morphological and behavioral changes. Besides the classical cAMP/PKA pathway, downstream of D1R, recent evidence implicates a cAMP-independent crosstalk mechanism by which the D1R potentiates NMDAR-mediated calcium influx and ERK activation. The mounting evidence of reciprocal modulation of DA and glutamate receptors adds further intricacy to striatal synaptic signaling and is liable to prove relevant for addictive drug-induced signaling, plasticity, and behavior. Herein, we review the evidence that built our understanding of the consequences of this synergistic signaling for the actions of drugs of abuse. Frontiers Media S.A. 2014-01-08 /pmc/articles/PMC3884214/ /pubmed/24409148 http://dx.doi.org/10.3389/fphar.2013.00172 Text en Copyright © 2014 Cahill, Salery, Vanhoutte and Caboche. http://creativecommons.org/licenses/by/3.0/ 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) or licensor 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 | Pharmacology Cahill, Emma Salery, Marine Vanhoutte, Peter Caboche, Jocelyne Convergence of dopamine and glutamate signaling onto striatal ERK activation in response to drugs of abuse |
title | Convergence of dopamine and glutamate signaling onto striatal ERK activation in response to drugs of abuse |
title_full | Convergence of dopamine and glutamate signaling onto striatal ERK activation in response to drugs of abuse |
title_fullStr | Convergence of dopamine and glutamate signaling onto striatal ERK activation in response to drugs of abuse |
title_full_unstemmed | Convergence of dopamine and glutamate signaling onto striatal ERK activation in response to drugs of abuse |
title_short | Convergence of dopamine and glutamate signaling onto striatal ERK activation in response to drugs of abuse |
title_sort | convergence of dopamine and glutamate signaling onto striatal erk activation in response to drugs of abuse |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884214/ https://www.ncbi.nlm.nih.gov/pubmed/24409148 http://dx.doi.org/10.3389/fphar.2013.00172 |
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