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Adaptive changes in the expression of central opioid receptors in mice lacking the dopamine D2 receptor gene
Abstract On the basis of numerous studies that have described interactions between the dopaminergic and opioidergic systems, we have investigated whether genetic deletion of dopamine D2 receptors (D2R) might influence the expression of central opioid receptors. The levels of mu, delta, kappa and noc...
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Published in: | Neuroscience 2008-05, Vol.153 (3), p.773-788 |
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description | Abstract On the basis of numerous studies that have described interactions between the dopaminergic and opioidergic systems, we have investigated whether genetic deletion of dopamine D2 receptors (D2R) might influence the expression of central opioid receptors. The levels of mu, delta, kappa and nociceptin opioid peptide receptors were determined in the brains and spinal cords of D2R knockout mice using quantitative autoradiography. The significant changes in opioid receptor binding found in the brains of heterozygous and homozygous mice were mainly restricted to the basal ganglia. In homozygous mice, a down-regulation of mu and delta receptors was observed in the striatal and pallidal areas. This alteration may be an adaptive response to the increase in enkephalin levels previously described in the striatum of these mutant mice. On the contrary, an up-regulation of kappa receptors was found in the striatal and nigral regions and might be related to a change in dynorphin levels. Significant increases in nociceptin receptor binding were also observed in homozygous mice in brain areas involved in motor behavior. At the spinal level, only kappa and nociceptin receptor binding showed significant overall differences between genotypes. The functional consequences of these adaptive changes are discussed in relation to the findings of behavioral and neurochemical studies reported to date in D2R knockout mice. |
doi_str_mv | 10.1016/j.neuroscience.2008.02.070 |
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The levels of mu, delta, kappa and nociceptin opioid peptide receptors were determined in the brains and spinal cords of D2R knockout mice using quantitative autoradiography. The significant changes in opioid receptor binding found in the brains of heterozygous and homozygous mice were mainly restricted to the basal ganglia. In homozygous mice, a down-regulation of mu and delta receptors was observed in the striatal and pallidal areas. This alteration may be an adaptive response to the increase in enkephalin levels previously described in the striatum of these mutant mice. On the contrary, an up-regulation of kappa receptors was found in the striatal and nigral regions and might be related to a change in dynorphin levels. Significant increases in nociceptin receptor binding were also observed in homozygous mice in brain areas involved in motor behavior. At the spinal level, only kappa and nociceptin receptor binding showed significant overall differences between genotypes. The functional consequences of these adaptive changes are discussed in relation to the findings of behavioral and neurochemical studies reported to date in D2R knockout mice.</description><identifier>ISSN: 0306-4522</identifier><identifier>EISSN: 1873-7544</identifier><identifier>DOI: 10.1016/j.neuroscience.2008.02.070</identifier><identifier>PMID: 18424009</identifier><identifier>CODEN: NRSCDN</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Adaptation, Physiological ; Animals ; Autoradiography ; basal ganglia ; Biological and medical sciences ; Brain - metabolism ; dopaminergic system ; Fundamental and applied biological sciences. Psychology ; knockout mice ; Male ; Mice ; Mice, Knockout ; Neurology ; opioidergic system ; Receptors, Dopamine D2 - deficiency ; Receptors, Dopamine D2 - genetics ; Receptors, Opioid - biosynthesis ; Receptors, Opioid - metabolism ; Spinal Cord - metabolism ; Vertebrates: nervous system and sense organs</subject><ispartof>Neuroscience, 2008-05, Vol.153 (3), p.773-788</ispartof><rights>IBRO</rights><rights>2008 IBRO</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-a3d478d5cf6dbdc6631af08af91e4171c2893f6779cdb9d590cbe4cbc21e8d053</citedby><cites>FETCH-LOGICAL-c463t-a3d478d5cf6dbdc6631af08af91e4171c2893f6779cdb9d590cbe4cbc21e8d053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20366219$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18424009$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Léna, I</creatorcontrib><creatorcontrib>Bradshaw, S</creatorcontrib><creatorcontrib>Pintar, J</creatorcontrib><creatorcontrib>Kitchen, I</creatorcontrib><title>Adaptive changes in the expression of central opioid receptors in mice lacking the dopamine D2 receptor gene</title><title>Neuroscience</title><addtitle>Neuroscience</addtitle><description>Abstract On the basis of numerous studies that have described interactions between the dopaminergic and opioidergic systems, we have investigated whether genetic deletion of dopamine D2 receptors (D2R) might influence the expression of central opioid receptors. The levels of mu, delta, kappa and nociceptin opioid peptide receptors were determined in the brains and spinal cords of D2R knockout mice using quantitative autoradiography. The significant changes in opioid receptor binding found in the brains of heterozygous and homozygous mice were mainly restricted to the basal ganglia. In homozygous mice, a down-regulation of mu and delta receptors was observed in the striatal and pallidal areas. This alteration may be an adaptive response to the increase in enkephalin levels previously described in the striatum of these mutant mice. On the contrary, an up-regulation of kappa receptors was found in the striatal and nigral regions and might be related to a change in dynorphin levels. Significant increases in nociceptin receptor binding were also observed in homozygous mice in brain areas involved in motor behavior. At the spinal level, only kappa and nociceptin receptor binding showed significant overall differences between genotypes. The functional consequences of these adaptive changes are discussed in relation to the findings of behavioral and neurochemical studies reported to date in D2R knockout mice.</description><subject>Adaptation, Physiological</subject><subject>Animals</subject><subject>Autoradiography</subject><subject>basal ganglia</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>dopaminergic system</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>knockout mice</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neurology</subject><subject>opioidergic system</subject><subject>Receptors, Dopamine D2 - deficiency</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Opioid - biosynthesis</subject><subject>Receptors, Opioid - metabolism</subject><subject>Spinal Cord - metabolism</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0306-4522</issn><issn>1873-7544</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqNkk1v1DAQhi0EosvCX0AWEtwSxo7zxQGpavmSKnEAzpZjT7beJnawk4r-e5xuVBAnfJnL885Yj15CXjHIGbDq7TF3uAQftUWnMecATQ48hxoekR1r6iKrSyEekx0UUGWi5PyMPIvxCOmVonhKzlgjuABod2Q4N2qa7S1Sfa3cASO1js7XSPHXFDBG6x31PdXo5qAG6ifrraEBNU6zD_f0aDXSQekb6w73UeMnNVqH9JI_kPSADp-TJ70aIr7Y5p78-Pjh-8Xn7Orrpy8X51eZFlUxZ6owom5MqfvKdEZXVcFUD43qW4aC1Uzzpi36qq5bbbrWlC3oDoXuNGfYGCiLPXlz2jsF_3PBOMvRRo3DoBz6JUoOrWCQRO3JuxOok84YsJdTsKMKd5KBXF3Lo_zbtVxdS-AyuU7hl9uVpRvR_IluchPwegNU1Grog3LaxgeOQ1FVnK3c5YnD5OTWYpDbOWOTvlkab__vP-__WaMH62y6fIN3GI9-CS5Zl0zGFJDf1nas5YAGoFhr8xsJSbpx</recordid><startdate>20080515</startdate><enddate>20080515</enddate><creator>Léna, I</creator><creator>Bradshaw, S</creator><creator>Pintar, J</creator><creator>Kitchen, I</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><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>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20080515</creationdate><title>Adaptive changes in the expression of central opioid receptors in mice lacking the dopamine D2 receptor gene</title><author>Léna, I ; Bradshaw, S ; Pintar, J ; Kitchen, I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-a3d478d5cf6dbdc6631af08af91e4171c2893f6779cdb9d590cbe4cbc21e8d053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adaptation, Physiological</topic><topic>Animals</topic><topic>Autoradiography</topic><topic>basal ganglia</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>dopaminergic system</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>knockout mice</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neurology</topic><topic>opioidergic system</topic><topic>Receptors, Dopamine D2 - deficiency</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Opioid - biosynthesis</topic><topic>Receptors, Opioid - metabolism</topic><topic>Spinal Cord - metabolism</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Léna, I</creatorcontrib><creatorcontrib>Bradshaw, S</creatorcontrib><creatorcontrib>Pintar, J</creatorcontrib><creatorcontrib>Kitchen, I</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Léna, I</au><au>Bradshaw, S</au><au>Pintar, J</au><au>Kitchen, I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adaptive changes in the expression of central opioid receptors in mice lacking the dopamine D2 receptor gene</atitle><jtitle>Neuroscience</jtitle><addtitle>Neuroscience</addtitle><date>2008-05-15</date><risdate>2008</risdate><volume>153</volume><issue>3</issue><spage>773</spage><epage>788</epage><pages>773-788</pages><issn>0306-4522</issn><eissn>1873-7544</eissn><coden>NRSCDN</coden><abstract>Abstract On the basis of numerous studies that have described interactions between the dopaminergic and opioidergic systems, we have investigated whether genetic deletion of dopamine D2 receptors (D2R) might influence the expression of central opioid receptors. The levels of mu, delta, kappa and nociceptin opioid peptide receptors were determined in the brains and spinal cords of D2R knockout mice using quantitative autoradiography. The significant changes in opioid receptor binding found in the brains of heterozygous and homozygous mice were mainly restricted to the basal ganglia. In homozygous mice, a down-regulation of mu and delta receptors was observed in the striatal and pallidal areas. This alteration may be an adaptive response to the increase in enkephalin levels previously described in the striatum of these mutant mice. On the contrary, an up-regulation of kappa receptors was found in the striatal and nigral regions and might be related to a change in dynorphin levels. Significant increases in nociceptin receptor binding were also observed in homozygous mice in brain areas involved in motor behavior. At the spinal level, only kappa and nociceptin receptor binding showed significant overall differences between genotypes. 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subjects | Adaptation, Physiological Animals Autoradiography basal ganglia Biological and medical sciences Brain - metabolism dopaminergic system Fundamental and applied biological sciences. Psychology knockout mice Male Mice Mice, Knockout Neurology opioidergic system Receptors, Dopamine D2 - deficiency Receptors, Dopamine D2 - genetics Receptors, Opioid - biosynthesis Receptors, Opioid - metabolism Spinal Cord - metabolism Vertebrates: nervous system and sense organs |
title | Adaptive changes in the expression of central opioid receptors in mice lacking the dopamine D2 receptor gene |
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