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The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice

Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 rece...

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Autores principales: Chesworth, Rose, Brown, Robyn M., Kim, Jee Hyun, Lawrence, Andrew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701637/
https://www.ncbi.nlm.nih.gov/pubmed/23861896
http://dx.doi.org/10.1371/journal.pone.0068371
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author Chesworth, Rose
Brown, Robyn M.
Kim, Jee Hyun
Lawrence, Andrew J.
author_facet Chesworth, Rose
Brown, Robyn M.
Kim, Jee Hyun
Lawrence, Andrew J.
author_sort Chesworth, Rose
collection PubMed
description Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5) in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO) mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience.
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spelling pubmed-37016372013-07-16 The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice Chesworth, Rose Brown, Robyn M. Kim, Jee Hyun Lawrence, Andrew J. PLoS One Research Article Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5) in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO) mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience. Public Library of Science 2013-07-04 /pmc/articles/PMC3701637/ /pubmed/23861896 http://dx.doi.org/10.1371/journal.pone.0068371 Text en © 2013 Chesworth 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
Chesworth, Rose
Brown, Robyn M.
Kim, Jee Hyun
Lawrence, Andrew J.
The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice
title The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice
title_full The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice
title_fullStr The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice
title_full_unstemmed The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice
title_short The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice
title_sort metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701637/
https://www.ncbi.nlm.nih.gov/pubmed/23861896
http://dx.doi.org/10.1371/journal.pone.0068371
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