Ethanol Induces Long-Term Facilitation of NR2B-NMDA Receptor Activity in the Dorsal Striatum: Implications for Alcohol Drinking Behavior
Addiction is characterized by compulsive alcohol or drug taking and seeking, and the dorsal striatum has been implicated in such maladaptive persistent habits. The NMDA receptor (NMDAR), which is a major target of alcohol, is implicated in striatal-based habit learning. We found that, in the dorsal...
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| Veröffentlicht in: | The Journal of neuroscience 2007-03, Vol.27 (13), p.3593-3602 |
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| creator | Wang, Jun Carnicella, Sebastien Phamluong, Khanhky Jeanblanc, Jerome Ronesi, Jennifer A Chaudhri, Nadia Janak, Patricia H Lovinger, David M Ron, Dorit |
| description | Addiction is characterized by compulsive alcohol or drug taking and seeking, and the dorsal striatum has been implicated in such maladaptive persistent habits. The NMDA receptor (NMDAR), which is a major target of alcohol, is implicated in striatal-based habit learning. We found that, in the dorsal striatum, alcohol (ethanol) exposure produced an increase in the phosphorylation of the NR2B subunit of the NMDAR, and a corresponding increase in the activity of Fyn kinase, which phosphorylates NR2B. We further observed an ethanol-mediated long-term facilitation (LTF) of the activity of NR2B-containing NMDARs (NR2B-NMDARs) in the dorsal striatum. This LTF is Fyn kinase dependent, because it was observed in Fyn wild-type but not in Fyn knock-out mice. Importantly, none of these biochemical and physiological changes was observed in the ventral striatum. Finally, dorsal but not ventral striatum infusion of a Fyn or NR2B-NMDAR inhibitor reduced rat operant self-administration of ethanol. Our results suggest that the Fyn-mediated phosphorylation and LTF of NR2B-NMDAR activity in the dorsal striatum after exposure to ethanol may underlie aberrant plasticity that contributes to mechanisms underlying alcohol drinking behavior. |
| doi_str_mv | 10.1523/JNEUROSCI.4749-06.2007 |
| format | Article |
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The NMDA receptor (NMDAR), which is a major target of alcohol, is implicated in striatal-based habit learning. We found that, in the dorsal striatum, alcohol (ethanol) exposure produced an increase in the phosphorylation of the NR2B subunit of the NMDAR, and a corresponding increase in the activity of Fyn kinase, which phosphorylates NR2B. We further observed an ethanol-mediated long-term facilitation (LTF) of the activity of NR2B-containing NMDARs (NR2B-NMDARs) in the dorsal striatum. This LTF is Fyn kinase dependent, because it was observed in Fyn wild-type but not in Fyn knock-out mice. Importantly, none of these biochemical and physiological changes was observed in the ventral striatum. Finally, dorsal but not ventral striatum infusion of a Fyn or NR2B-NMDAR inhibitor reduced rat operant self-administration of ethanol. Our results suggest that the Fyn-mediated phosphorylation and LTF of NR2B-NMDAR activity in the dorsal striatum after exposure to ethanol may underlie aberrant plasticity that contributes to mechanisms underlying alcohol drinking behavior.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.4749-06.2007</identifier><identifier>PMID: 17392475</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Alcohol Drinking - physiopathology ; Alcohol Drinking - psychology ; Animals ; Behavior, Addictive - physiopathology ; Conditioning, Operant ; Corpus Striatum - drug effects ; Ethanol - pharmacology ; In Vitro Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuronal Plasticity - drug effects ; Neurotransmitter Agents - metabolism ; Nucleus Accumbens - drug effects ; Patch-Clamp Techniques ; Phosphorylation ; Proto-Oncogene Proteins c-fyn - metabolism ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate - drug effects ; Receptors, N-Methyl-D-Aspartate - metabolism ; Self Administration ; Social Facilitation</subject><ispartof>The Journal of neuroscience, 2007-03, Vol.27 (13), p.3593-3602</ispartof><rights>Copyright © 2007 Society for Neuroscience 0270-6474/07/273593-10$15.00/0 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-d4a051ff4e8775cccf1a9df7b00b04ff0c39f03ff335dd6654629fb5e68be7273</citedby><cites>FETCH-LOGICAL-c594t-d4a051ff4e8775cccf1a9df7b00b04ff0c39f03ff335dd6654629fb5e68be7273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672130/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672130/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17392475$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Carnicella, Sebastien</creatorcontrib><creatorcontrib>Phamluong, Khanhky</creatorcontrib><creatorcontrib>Jeanblanc, Jerome</creatorcontrib><creatorcontrib>Ronesi, Jennifer A</creatorcontrib><creatorcontrib>Chaudhri, Nadia</creatorcontrib><creatorcontrib>Janak, Patricia H</creatorcontrib><creatorcontrib>Lovinger, David M</creatorcontrib><creatorcontrib>Ron, Dorit</creatorcontrib><title>Ethanol Induces Long-Term Facilitation of NR2B-NMDA Receptor Activity in the Dorsal Striatum: Implications for Alcohol Drinking Behavior</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Addiction is characterized by compulsive alcohol or drug taking and seeking, and the dorsal striatum has been implicated in such maladaptive persistent habits. 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Our results suggest that the Fyn-mediated phosphorylation and LTF of NR2B-NMDAR activity in the dorsal striatum after exposure to ethanol may underlie aberrant plasticity that contributes to mechanisms underlying alcohol drinking behavior.</description><subject>Alcohol Drinking - physiopathology</subject><subject>Alcohol Drinking - psychology</subject><subject>Animals</subject><subject>Behavior, Addictive - physiopathology</subject><subject>Conditioning, Operant</subject><subject>Corpus Striatum - drug effects</subject><subject>Ethanol - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Neuronal Plasticity - drug effects</subject><subject>Neurotransmitter Agents - metabolism</subject><subject>Nucleus Accumbens - drug effects</subject><subject>Patch-Clamp Techniques</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins c-fyn - metabolism</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, N-Methyl-D-Aspartate - drug effects</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Self Administration</subject><subject>Social Facilitation</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1uEzEURkcIREPhFSqvYDWpf2bsmgVSmqQlKKRS2q4tj8fOGDzjYHsS9Q14bCYkKrBi5cU933d9dbLsAsExKjG5_LKaP67v7qeLccEKnkM6xhCyF9lomPIcFxC9zEYQM5jTATjL3sT4DQ4EROx1doYY4bhg5Sj7OU-N7LwDi67ulY5g6btN_qBDC26kss4mmazvgDdgtcbX-errbALWWult8gFMVLI7m56A7UBqNJj5EKUD9ylYmfr2I1i0W2fV74oIzCHhlG-GdbNgu--224Br3cid9eFt9spIF_W703uePd7MH6af8-Xd7WI6Weaq5EXK60LCEhlT6CvGSqWUQZLXhlUQVrAwBirCDSTGEFLWNaVlQTE3VanpVaUZZuQ8-3Ts3fZVq2uluxSkE9tgWxmehJdW_DvpbCM2ficoZRgROBS8PxUE_6PXMYnWRqWdk532fRQMEsQpZ_8FB4oWJaQDSI-gCj7GoM3zbxAUB9vi2bY42BaQioPtIXjx9y1_Yie9A_DhCDR20-xt0CK20rkBR2K_32MmEBGk5IT8Aumitws</recordid><startdate>20070328</startdate><enddate>20070328</enddate><creator>Wang, Jun</creator><creator>Carnicella, Sebastien</creator><creator>Phamluong, Khanhky</creator><creator>Jeanblanc, Jerome</creator><creator>Ronesi, Jennifer A</creator><creator>Chaudhri, Nadia</creator><creator>Janak, Patricia H</creator><creator>Lovinger, David M</creator><creator>Ron, Dorit</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</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>7QG</scope><scope>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070328</creationdate><title>Ethanol Induces Long-Term Facilitation of NR2B-NMDA Receptor Activity in the Dorsal Striatum: Implications for Alcohol Drinking Behavior</title><author>Wang, Jun ; Carnicella, Sebastien ; Phamluong, Khanhky ; Jeanblanc, Jerome ; Ronesi, Jennifer A ; Chaudhri, Nadia ; Janak, Patricia H ; Lovinger, David M ; Ron, Dorit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-d4a051ff4e8775cccf1a9df7b00b04ff0c39f03ff335dd6654629fb5e68be7273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Alcohol Drinking - physiopathology</topic><topic>Alcohol Drinking - psychology</topic><topic>Animals</topic><topic>Behavior, Addictive - physiopathology</topic><topic>Conditioning, Operant</topic><topic>Corpus Striatum - drug effects</topic><topic>Ethanol - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Neuronal Plasticity - drug effects</topic><topic>Neurotransmitter Agents - metabolism</topic><topic>Nucleus Accumbens - drug effects</topic><topic>Patch-Clamp Techniques</topic><topic>Phosphorylation</topic><topic>Proto-Oncogene Proteins c-fyn - metabolism</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, N-Methyl-D-Aspartate - drug effects</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Self Administration</topic><topic>Social Facilitation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Carnicella, Sebastien</creatorcontrib><creatorcontrib>Phamluong, Khanhky</creatorcontrib><creatorcontrib>Jeanblanc, Jerome</creatorcontrib><creatorcontrib>Ronesi, Jennifer A</creatorcontrib><creatorcontrib>Chaudhri, Nadia</creatorcontrib><creatorcontrib>Janak, Patricia H</creatorcontrib><creatorcontrib>Lovinger, David M</creatorcontrib><creatorcontrib>Ron, Dorit</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jun</au><au>Carnicella, Sebastien</au><au>Phamluong, Khanhky</au><au>Jeanblanc, Jerome</au><au>Ronesi, Jennifer A</au><au>Chaudhri, Nadia</au><au>Janak, Patricia H</au><au>Lovinger, David M</au><au>Ron, Dorit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ethanol Induces Long-Term Facilitation of NR2B-NMDA Receptor Activity in the Dorsal Striatum: Implications for Alcohol Drinking Behavior</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2007-03-28</date><risdate>2007</risdate><volume>27</volume><issue>13</issue><spage>3593</spage><epage>3602</epage><pages>3593-3602</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><abstract>Addiction is characterized by compulsive alcohol or drug taking and seeking, and the dorsal striatum has been implicated in such maladaptive persistent habits. The NMDA receptor (NMDAR), which is a major target of alcohol, is implicated in striatal-based habit learning. We found that, in the dorsal striatum, alcohol (ethanol) exposure produced an increase in the phosphorylation of the NR2B subunit of the NMDAR, and a corresponding increase in the activity of Fyn kinase, which phosphorylates NR2B. We further observed an ethanol-mediated long-term facilitation (LTF) of the activity of NR2B-containing NMDARs (NR2B-NMDARs) in the dorsal striatum. This LTF is Fyn kinase dependent, because it was observed in Fyn wild-type but not in Fyn knock-out mice. Importantly, none of these biochemical and physiological changes was observed in the ventral striatum. Finally, dorsal but not ventral striatum infusion of a Fyn or NR2B-NMDAR inhibitor reduced rat operant self-administration of ethanol. Our results suggest that the Fyn-mediated phosphorylation and LTF of NR2B-NMDAR activity in the dorsal striatum after exposure to ethanol may underlie aberrant plasticity that contributes to mechanisms underlying alcohol drinking behavior.</abstract><cop>United States</cop><pub>Soc Neuroscience</pub><pmid>17392475</pmid><doi>10.1523/JNEUROSCI.4749-06.2007</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alcohol Drinking - physiopathology Alcohol Drinking - psychology Animals Behavior, Addictive - physiopathology Conditioning, Operant Corpus Striatum - drug effects Ethanol - pharmacology In Vitro Techniques Male Mice Mice, Inbred C57BL Mice, Transgenic Neuronal Plasticity - drug effects Neurotransmitter Agents - metabolism Nucleus Accumbens - drug effects Patch-Clamp Techniques Phosphorylation Proto-Oncogene Proteins c-fyn - metabolism Rats Rats, Long-Evans Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate - drug effects Receptors, N-Methyl-D-Aspartate - metabolism Self Administration Social Facilitation |
| title | Ethanol Induces Long-Term Facilitation of NR2B-NMDA Receptor Activity in the Dorsal Striatum: Implications for Alcohol Drinking Behavior |
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