Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers.
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.
Bannon
Michael J
MJ
Department of Psychiatry and Behavioral Neurosciences, Pharmacology, and Pathology, Wayne State University School of Medicine, 2309 Scott Hall, 540 East Canfield Avenue, Detroit, MI 48201, USA. mbannon@med.wayne.edu
Pruetz
Barb
B
Manning-Bog
Amy B
AB
Whitty
Christopher J
CJ
Michelhaugh
Sharon K
SK
Sacchetti
Paola
P
Granneman
James G
JG
Mash
Deborah C
DC
Schmidt
Carl J
CJ
D000328:Adult; D001344:Autopsy; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D003042:Cocaine / Q000009:adverse effects*; D004268:DNA-Binding Proteins; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D009293:Opioid-Related Disorders / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D019966:Substance-Related Disorders; D014157:Transcription Factors / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C539882:NR4A2 protein, human; D009419:Nerve Tissue Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; C493214:SLC6A3 protein, human; D014157:Transcription Factors; D003042:Cocaine; D004298:Dopamine