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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3701637?pdf=render |
| _version_ | 1818325503290900480 |
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| author | Rose Chesworth Robyn M Brown Jee Hyun Kim Andrew J Lawrence |
| author_facet | Rose Chesworth Robyn M Brown Jee Hyun Kim Andrew J Lawrence |
| author_sort | Rose Chesworth |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T11:45:31Z |
| format | Article |
| id | doaj.art-5d17249092474bef9304330e40e64628 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T11:45:31Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5d17249092474bef9304330e40e646282022-12-21T23:47:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6837110.1371/journal.pone.0068371The metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice.Rose ChesworthRobyn M BrownJee Hyun KimAndrew J LawrenceMethamphetamine (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.http://europepmc.org/articles/PMC3701637?pdf=render |
| spellingShingle | Rose Chesworth Robyn M Brown Jee Hyun Kim Andrew J Lawrence The metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3701637?pdf=render |
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