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LIBRIS Formathandbok  (Information om MARC21)
00005218naa a2200769 4500
008100923s2008 | |||||||||||000 ||eng|
024a urn:nbn:se:liu:diva-596972 urn
024a https://doi.org/10.1073/pnas.08039591052 DOI
024a http://kipublications.ki.se/Default.aspx?queryparsed=id:1178854212 URI
040 a (SwePub)liud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Bilbao, Ainhoau Central Institute of Mental Health, Mannheim4 aut
2451 0a Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine
264 1b National Academy of Sciences; 1999,c 2008
338 a print2 rdacarrier
506 a gratis
520 a The persistent nature of addiction has been associated with activity-induced plasticity of neurons within the striatum and nucleus accumbens (NAc). To identify the molecular processes leading to these adaptations, we performed Cre/loxP-mediated genetic ablations of two key regulators of gene expression in response to activity, the Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) and its postulated main target, the cAMP-responsive element binding protein (CREB). We found that acute cocaine-induced gene expression in the striatum was largely unaffected by the loss of CaMKIV. On the behavioral level, mice lacking CaMKIV in dopaminoceptive neurons displayed increased sensitivity to cocaine as evidenced by augmented expression of locomotor sensitization and enhanced conditioned place preference and reinstatement after extinction. However, the loss of CREB in the forebrain had no effect on either of these behaviors, even though it robustly blunted acute cocaine-induced transcription. To test the relevance of these observations for addiction in humans, we performed an association study of CAMK4 and CREB promoter polymorphisms with cocaine addiction in a large sample of addicts. We found that a single nucleotide polymorphism in the CAMK4 promoter was significantly associated with cocaine addiction, whereas variations in the CREB promoter regions did not correlate with drug abuse. These findings reveal a critical role for CaMKIV in the development and persistence of cocaine-induced behaviors, through mechanisms dissociated from acute effects on gene expression and CREB-dependent transcription.
653 a addiction; CaMKIV; CREB; striatum
700a Rodriguez Parkitna, Janu German Cancer Research Center, Heidelberg4 aut
700a Engblom, Davidu German Cancer Research Center, Heidelberg4 aut0 (Swepub:liu)daven69
700a Perreau-Lenz, Stephanieu Central Institute of Mental Health, Mannheim4 aut
700a Sanchis-Segura, Carlesu Central Institute of Mental Health, Mannheim4 aut
700a Schneider, Miriamu Central Institute of Mental Health, Mannheim4 aut
700a Konopka, Witoldu German Cancer Research Center, Heidelberg4 aut
700a Westphal, Magdalenau German Cancer Research Center, Heidelberg4 aut
700a Breen, Geromeu King's College London4 aut
700a Desrivieres, Sylvaneu King's College London4 aut
700a Klugmann, Matthiasu University of Mainz4 aut
700a Guindalini, Camilau Universidade Federal de São Paulo4 aut
700a Vallada, Homerou Universidade de São Paulo4 aut
700a Laranjeira, Ronaldou Universidade Federal de São Paulo4 aut
700a Rodriguez de Fonseca, Fernandou Hospital Carlos Haya4 aut
700a Schumann, Gunteru King's College London4 aut
700a Schuetz, Guentheru Central Institute of Mental Health, Mannheim4 aut
700a Spanagel, Raineru Central Institute of Mental Health, J5, 68159 Mannheim4 aut
700a Sanchis-Segura, C4 aut
700a Schneider, M4 aut
700a Bilbao, A4 aut
700a Parkitna, JR4 aut
700a Vallada, Hu Karolinska Institutet4 aut
700a Konopka, W4 aut
700a Klugmann, M4 aut
700a Westphal, M4 aut
700a Breen, G4 aut
700a Spanagel, R4 aut
700a Laranjeira, R4 aut
700a Perreau-Lenz, S4 aut
700a de Fonseca, FR4 aut
700a Schutz, G4 aut
700a Schumann, G4 aut
700a Engblom, D4 aut
700a Guindalini, C4 aut
700a Desrivieres, S4 aut
710a Central Institute of Mental Health, Mannheimb German Cancer Research Center, Heidelberg4 org
773t Proceedings of the National Academy of Sciences of the United States of Americad : National Academy of Sciences; 1999g 105:45, s. 17549-17554q 105:45<17549-17554x 0027-8424x 1091-6490
856u http://www.pnas.org/content/105/45/17549.full.pdf
8564 8u http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-59697x lärosäteslänky Till lärosätets (liu) databas
8564 8u https://doi.org/10.1073/pnas.0803959105
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:117885421

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