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mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine
Adenosine A2A receptors and metabotropic glutamate type 5 (mGlu5) receptors are co-localized in the striatum and can functionally interact to regulate drug-seeking. We further explored this interaction using antagonism of mGlu5 receptors with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) in...
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| Published in: | The international journal of neuropsychopharmacology 2012-08, Vol.15 (7), p.995-1001 |
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| cites | cdi_FETCH-LOGICAL-c303t-785c7cdf8c0d4d68578542dd0b7e86cac3f43e2ecb1e6899b46811a129c7a1ff3 |
| container_end_page | 1001 |
| container_issue | 7 |
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| container_title | The international journal of neuropsychopharmacology |
| container_volume | 15 |
| creator | Brown, Robyn M. Duncan, Jhodie R. Stagnitti, Monique R. Ledent, Catherine Lawrence, Andrew J. |
| description | Adenosine A2A receptors and metabotropic glutamate type 5 (mGlu5) receptors are co-localized in the striatum and can functionally interact to regulate drug-seeking. We further explored this interaction using antagonism of mGlu5 receptors with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) in combination with genetic deletion of A2A receptors. The conditioned rewarding and locomotor-activating properties of cocaine were evaluated via conditioned place preference (CPP). Vehicle-treated mice of both genotypes expressed a CPP to cocaine while MTEP abolished cocaine CPP in wild-type, but not A2A knockout, mice. These results were mirrored when conditioned hyperactivity was assessed. In contrast, MTEP attenuated the acute locomotor-activating properties of cocaine similarly in both genotypes. These data provide evidence for a functional interaction between adenosine A2A and mGlu5 receptors in mediating the conditioned effects of cocaine but not direct cocaine-induced hyperactivity. This functional interaction is supported by modulation of 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([125I]ZM241385) binding to the A2A receptor by MTEP. |
| doi_str_mv | 10.1017/S146114571100126X |
| format | article |
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This functional interaction is supported by modulation of 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([125I]ZM241385) binding to the A2A receptor by MTEP.</description><identifier>ISSN: 1461-1457</identifier><identifier>EISSN: 1469-5111</identifier><identifier>DOI: 10.1017/S146114571100126X</identifier><identifier>PMID: 21816123</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Analysis of Variance ; Animals ; Autoradiography ; Brain - diagnostic imaging ; Brain - drug effects ; Brain - metabolism ; Cocaine - pharmacology ; Conditioning, Operant - drug effects ; Conditioning, Operant - physiology ; Dopamine Uptake Inhibitors - pharmacology ; Drug Interactions ; Excitatory Amino Acid Antagonists - pharmacology ; Iodine Isotopes - pharmacokinetics ; Locomotion - drug effects ; Locomotion - genetics ; Male ; Mice ; Mice, Knockout ; Protein Binding - drug effects ; Protein Binding - genetics ; Pyridines - pharmacology ; Radionuclide Imaging ; Receptor, Adenosine A2A - deficiency ; Receptor, Adenosine A2A - metabolism ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate - metabolism ; Thiazoles - pharmacology ; Time Factors ; Triazines - pharmacokinetics ; Triazoles - pharmacokinetics</subject><ispartof>The international journal of neuropsychopharmacology, 2012-08, Vol.15 (7), p.995-1001</ispartof><rights>CINP 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c303t-785c7cdf8c0d4d68578542dd0b7e86cac3f43e2ecb1e6899b46811a129c7a1ff3</citedby><cites>FETCH-LOGICAL-c303t-785c7cdf8c0d4d68578542dd0b7e86cac3f43e2ecb1e6899b46811a129c7a1ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21816123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brown, Robyn M.</creatorcontrib><creatorcontrib>Duncan, Jhodie R.</creatorcontrib><creatorcontrib>Stagnitti, Monique R.</creatorcontrib><creatorcontrib>Ledent, Catherine</creatorcontrib><creatorcontrib>Lawrence, Andrew J.</creatorcontrib><title>mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine</title><title>The international journal of neuropsychopharmacology</title><addtitle>Int J Neuropsychopharmacol</addtitle><description>Adenosine A2A receptors and metabotropic glutamate type 5 (mGlu5) receptors are co-localized in the striatum and can functionally interact to regulate drug-seeking. 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This functional interaction is supported by modulation of 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([125I]ZM241385) binding to the A2A receptor by MTEP.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Autoradiography</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cocaine - pharmacology</subject><subject>Conditioning, Operant - drug effects</subject><subject>Conditioning, Operant - physiology</subject><subject>Dopamine Uptake Inhibitors - pharmacology</subject><subject>Drug Interactions</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Iodine Isotopes - pharmacokinetics</subject><subject>Locomotion - drug effects</subject><subject>Locomotion - genetics</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Protein Binding - drug effects</subject><subject>Protein Binding - genetics</subject><subject>Pyridines - pharmacology</subject><subject>Radionuclide Imaging</subject><subject>Receptor, Adenosine A2A - deficiency</subject><subject>Receptor, Adenosine A2A - metabolism</subject><subject>Receptor, Metabotropic Glutamate 5</subject><subject>Receptors, Metabotropic Glutamate - metabolism</subject><subject>Thiazoles - pharmacology</subject><subject>Time Factors</subject><subject>Triazines - pharmacokinetics</subject><subject>Triazoles - pharmacokinetics</subject><issn>1461-1457</issn><issn>1469-5111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp1kE1LxDAURYMofv8ANxJw46aalzRpuxzELxBcqKCrkiYvWmmbMWkX_nszziiiuEo4Oe--cAk5AHYCDIrTO8gVQC4LAMaAq8c1sp1QlUkAWP-8Q7Z43yI7Mb4yxnMp1CbZ4lCCAi62yVN_2U2S6sFSbXHwsR2QzviMBjQ4H32g7TBi0GZs_RATfZ46PSIdX5AaP9h2wdFSdA7NGKl3CRudUvbIhtNdxP3VuUseLs7vz66ym9vL67PZTWYEE2NWlNIUxrrSMJtbVcoEcm4tawosldFGuFwgR9MAqrKqmlyVABp4ZQoNzoldcrzMnQf_NmEc676NBrtOD-inWAMTjBUyFyqpR7_UVz-FIf0uWbwqlZCSJQuWlgk-xoCunoe21-E9SfWi9_pP72nmcJU8NT3a74mvopMgVqG6b0Jrn_Hn7v9iPwB_9IwM</recordid><startdate>201208</startdate><enddate>201208</enddate><creator>Brown, Robyn M.</creator><creator>Duncan, Jhodie R.</creator><creator>Stagnitti, Monique R.</creator><creator>Ledent, Catherine</creator><creator>Lawrence, Andrew J.</creator><general>Cambridge University Press</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>201208</creationdate><title>mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine</title><author>Brown, Robyn M. ; Duncan, Jhodie R. ; Stagnitti, Monique R. ; Ledent, Catherine ; Lawrence, Andrew J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c303t-785c7cdf8c0d4d68578542dd0b7e86cac3f43e2ecb1e6899b46811a129c7a1ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Autoradiography</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cocaine - pharmacology</topic><topic>Conditioning, Operant - drug effects</topic><topic>Conditioning, Operant - physiology</topic><topic>Dopamine Uptake Inhibitors - pharmacology</topic><topic>Drug Interactions</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Iodine Isotopes - pharmacokinetics</topic><topic>Locomotion - drug effects</topic><topic>Locomotion - genetics</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Protein Binding - drug effects</topic><topic>Protein Binding - genetics</topic><topic>Pyridines - pharmacology</topic><topic>Radionuclide Imaging</topic><topic>Receptor, Adenosine A2A - deficiency</topic><topic>Receptor, Adenosine A2A - metabolism</topic><topic>Receptor, Metabotropic Glutamate 5</topic><topic>Receptors, Metabotropic Glutamate - metabolism</topic><topic>Thiazoles - pharmacology</topic><topic>Time Factors</topic><topic>Triazines - pharmacokinetics</topic><topic>Triazoles - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brown, Robyn M.</creatorcontrib><creatorcontrib>Duncan, Jhodie R.</creatorcontrib><creatorcontrib>Stagnitti, Monique R.</creatorcontrib><creatorcontrib>Ledent, Catherine</creatorcontrib><creatorcontrib>Lawrence, Andrew J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>The international journal of neuropsychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brown, Robyn M.</au><au>Duncan, Jhodie R.</au><au>Stagnitti, Monique R.</au><au>Ledent, Catherine</au><au>Lawrence, Andrew J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine</atitle><jtitle>The international journal of neuropsychopharmacology</jtitle><addtitle>Int J Neuropsychopharmacol</addtitle><date>2012-08</date><risdate>2012</risdate><volume>15</volume><issue>7</issue><spage>995</spage><epage>1001</epage><pages>995-1001</pages><issn>1461-1457</issn><eissn>1469-5111</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Adenosine A2A receptors and metabotropic glutamate type 5 (mGlu5) receptors are co-localized in the striatum and can functionally interact to regulate drug-seeking. We further explored this interaction using antagonism of mGlu5 receptors with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) in combination with genetic deletion of A2A receptors. The conditioned rewarding and locomotor-activating properties of cocaine were evaluated via conditioned place preference (CPP). Vehicle-treated mice of both genotypes expressed a CPP to cocaine while MTEP abolished cocaine CPP in wild-type, but not A2A knockout, mice. These results were mirrored when conditioned hyperactivity was assessed. In contrast, MTEP attenuated the acute locomotor-activating properties of cocaine similarly in both genotypes. These data provide evidence for a functional interaction between adenosine A2A and mGlu5 receptors in mediating the conditioned effects of cocaine but not direct cocaine-induced hyperactivity. This functional interaction is supported by modulation of 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([125I]ZM241385) binding to the A2A receptor by MTEP.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>21816123</pmid><doi>10.1017/S146114571100126X</doi><tpages>7</tpages></addata></record> |
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| ispartof | The international journal of neuropsychopharmacology, 2012-08, Vol.15 (7), p.995-1001 |
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| language | eng |
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| source | Oxford University Press Journals |
| subjects | Analysis of Variance Animals Autoradiography Brain - diagnostic imaging Brain - drug effects Brain - metabolism Cocaine - pharmacology Conditioning, Operant - drug effects Conditioning, Operant - physiology Dopamine Uptake Inhibitors - pharmacology Drug Interactions Excitatory Amino Acid Antagonists - pharmacology Iodine Isotopes - pharmacokinetics Locomotion - drug effects Locomotion - genetics Male Mice Mice, Knockout Protein Binding - drug effects Protein Binding - genetics Pyridines - pharmacology Radionuclide Imaging Receptor, Adenosine A2A - deficiency Receptor, Adenosine A2A - metabolism Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate - metabolism Thiazoles - pharmacology Time Factors Triazines - pharmacokinetics Triazoles - pharmacokinetics |
| title | mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine |
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