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Sökning: onr:"swepub:oai:DiVA.org:liu-59697" > Loss of the Ca2+/ca...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004595naa a2200553 4500
001oai:DiVA.org:liu-59697
003SwePub
008100923s2008 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:117885421
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-596972 URI
0247 a https://doi.org/10.1073/pnas.08039591052 DOI
0247 a 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
1001 a 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 c 2008-11-11
264 1b National Academy of Sciences; 1999,c 2008
338 a print2 rdacarrier
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
653 a MEDICINE
653 a MEDICIN
7001 a Rodriguez Parkitna, Janu German Cancer Research Center, Heidelberg4 aut
7001 a Engblom, Davidu German Cancer Research Center, Heidelberg4 aut0 (Swepub:liu)daven69
7001 a Perreau-Lenz, Stephanieu Central Institute of Mental Health, Mannheim4 aut
7001 a Sanchis-Segura, Carlesu Central Institute of Mental Health, Mannheim4 aut
7001 a Schneider, Miriamu Central Institute of Mental Health, Mannheim4 aut
7001 a Konopka, Witoldu German Cancer Research Center, Heidelberg4 aut
7001 a Westphal, Magdalenau German Cancer Research Center, Heidelberg4 aut
7001 a Breen, Geromeu King's College London4 aut
7001 a Desrivieres, Sylvaneu King's College London4 aut
7001 a Klugmann, Matthiasu University of Mainz4 aut
7001 a Guindalini, Camilau Universidade Federal de São Paulo4 aut
7001 a Vallada, Homerou Karolinska Institutet,Universidade de São Paulo4 aut
7001 a Laranjeira, Ronaldou Universidade Federal de São Paulo4 aut
7001 a Rodriguez de Fonseca, Fernandou Hospital Carlos Haya4 aut
7001 a Schumann, Gunteru King's College London4 aut
7001 a Schuetz, Guentheru Central Institute of Mental Health, Mannheim4 aut
7001 a Spanagel, Raineru Central Institute of Mental Health, J5, 68159 Mannheim4 aut
7102 a Central Institute of Mental Health, Mannheimb German Cancer Research Center, Heidelberg4 org
7730 t 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
8564 u http://www.pnas.org/content/105/45/17549.full.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-59697
8564 8u https://doi.org/10.1073/pnas.0803959105
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:117885421

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