Chronic cocaine administration modulates the expression of transcription factors involved in midbrain dopaminergic neuron function.
Chronic cocaine use leads to pronounced alterations in neuronal functions in brain circuits associated with reward. In the present study, we examined in the rat midbrain the effects of acute, subchronic (5 days) and chronic cocaine treatments (14 days) on the gene expression of transcription factors involved in the development and maintenance of dopaminergic neurons. We show that chronic, but not acute or subchronic, cocaine administration downregulates Nurr1 and Pitx3 transcripts whereas En1 transcripts are upregulated. Conversely, Lmx1b and En2 transcripts are not affected by the drug treatment, indicating that the modulation of the midbrain transcription factors analyzed is highly selective. Interestingly, modification of the gene expression for these transcription factors persists in midbrain as long as two weeks after the last drug administration, suggesting that it may account for some of the enduring alterations in midbrain dopaminergic circuits associated with chronic cocaine use.
Leo
D
D
Institute of Genetics and Biophysics A. Buzzati Traverso, CNR, Via Pietro Castellino, 111, 80131-Naples, Italy.
di Porzio
U
U
Racagni
G
G
Riva
M A
MA
Fumagalli
F
F
Perrone-Capano
C
C
D000818:Animals; D015153:Blotting, Western; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000099266:Engrailed 2 Protein
D003042:Cocaine; D004268:DNA-Binding Proteins; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D000099266:Engrailed 2 Protein; C112149:LIM homeobox transcription factor 1 beta; C539884:Nr4a2 protein, rat; C433629:homeobox protein PITX3