Molecular profiling of midbrain dopamine regions in cocaine overdose victims

Wen Xue Tang, Wendy H. Fasulo, Deborah C Mash, Scott E. Hemby

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in neuronal function in brain regions associated with drug reinforcement. To evaluate whether the alterations in gene expression in cocaine overdose victims are associated with specific dopamine populations in the midbrain, cDNA arrays and western blotting were used to compare gene and protein expression patterns between cocaine overdose victims and age-matched controls in the ventral tegmental area (VTA) and lateral substantia nigra (I-SN). Array analysis revealed significant up-regulation of numerous transcripts in the VTA, but not in the I-SN, of cocaine overdose victims including NMDAR1, GluR2, GluR5 and KA2 receptor mRNA (p < 0.05). No significant alterations between overdose victims and controls were observed for GluR1, R3 or R4 mRNA levels. Correspondingly, western blot analysis revealed VTA-selective up-regulation of CREB (p < 0.01), NMDAR1 (p < 0.01), GluR2 (p < 0.05), GluR5 (p < 0.01) and KA2 (p < 0.05) protein levels of cocaine overdose victims. The present results indicate that selective alterations of CREB and certain ionotropic glutamate receptor (iGluR) subtypes appear to be associated with chronic cocaine use in humans in a region-specific manner. Moreover, as subunit composition determines the functional properties of iGluRs, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long-term biochemical and behavioral effects of cocaine in humans.

Original languageEnglish
Pages (from-to)911-924
Number of pages14
JournalJournal of Neurochemistry
Volume85
Issue number4
StatePublished - May 1 2003

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Mesencephalon
Cocaine
Dopamine
Ventral Tegmental Area
Up-Regulation
Western Blotting
Ionotropic Glutamate Receptors
Gene Expression
Messenger RNA
Substantia Nigra
Oligonucleotide Array Sequence Analysis
Gene expression
Brain
Reinforcement
Animals
Proteins
Animal Models
Complementary DNA
Chemical analysis
Pharmaceutical Preparations

Keywords

  • Cocaine
  • CREB
  • Gene expression
  • Glutamate
  • Substantia nigra
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Tang, W. X., Fasulo, W. H., Mash, D. C., & Hemby, S. E. (2003). Molecular profiling of midbrain dopamine regions in cocaine overdose victims. Journal of Neurochemistry, 85(4), 911-924.

Molecular profiling of midbrain dopamine regions in cocaine overdose victims. / Tang, Wen Xue; Fasulo, Wendy H.; Mash, Deborah C; Hemby, Scott E.

In: Journal of Neurochemistry, Vol. 85, No. 4, 01.05.2003, p. 911-924.

Research output: Contribution to journalArticle

Tang, WX, Fasulo, WH, Mash, DC & Hemby, SE 2003, 'Molecular profiling of midbrain dopamine regions in cocaine overdose victims', Journal of Neurochemistry, vol. 85, no. 4, pp. 911-924.
Tang WX, Fasulo WH, Mash DC, Hemby SE. Molecular profiling of midbrain dopamine regions in cocaine overdose victims. Journal of Neurochemistry. 2003 May 1;85(4):911-924.
Tang, Wen Xue ; Fasulo, Wendy H. ; Mash, Deborah C ; Hemby, Scott E. / Molecular profiling of midbrain dopamine regions in cocaine overdose victims. In: Journal of Neurochemistry. 2003 ; Vol. 85, No. 4. pp. 911-924.
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