Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers

Michael J. Bannon, Barb Pruetz, Amy B. Manning-Bog, Christopher J. Whitty, Sharon K. Michelhaugh, Paola Sacchetti, James G. Granneman, Deborah C. Mash, Carl J. Schmidt

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75 Scopus citations

Abstract

Chronic exposure to cocaine induces long-term adaptations that are likely to involve changes in transcription factor expression. This possibility has not been examined in the cocaine-exposed human brain. The transcription factor nurr1 is highly expressed in rodent midbrain dopamine neurons and is essential for their proper phenotypic development. Here we show that human NURR1 gene expression is robust within control subjects and reduced markedly within the dopamine neurons of human cocaine abusers. NURR1 is known to regulate transcription of the gene encoding the cocaine-sensitive dopamine transporter (DAT). We show here that DAT gene expression also is reduced markedly in the dopamine neurons of NURR1-deficient cocaine abusers, suggesting that NURR1 plays a critical role in vivo in controlling human DAT gene expression and adaptation to repeated exposure to cocaine.

Original languageEnglish (US)
Pages (from-to)6382-6385
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number9
DOIs
StatePublished - Apr 30 2002

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    Bannon, M. J., Pruetz, B., Manning-Bog, A. B., Whitty, C. J., Michelhaugh, S. K., Sacchetti, P., Granneman, J. G., Mash, D. C., & Schmidt, C. J. (2002). Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers. Proceedings of the National Academy of Sciences of the United States of America, 99(9), 6382-6385. https://doi.org/10.1073/pnas.092654299