Repeated cocaine administration alters the expression of genes in corticolimbic circuitry after a 3-week withdrawal: a DNA macroarray study
Article first published online: 3 FEB 2004
Journal of Neurochemistry
Volume 82, Issue 5, pages 1290–1299, September 2002
How to Cite
Toda, S., McGinty, J. F. and Kalivas, P. W. (2002), Repeated cocaine administration alters the expression of genes in corticolimbic circuitry after a 3-week withdrawal: a DNA macroarray study. Journal of Neurochemistry, 82: 1290–1299. doi: 10.1046/j.1471-4159.2002.01083.x
- Issue published online: 3 FEB 2004
- Article first published online: 3 FEB 2004
- Received May 3, 2002; revised manuscript received June 5, 2002; accepted June 6, 2002.
- adenosine A1 receptor;
- cDNA array;
- glutamate receptor 5;
- neuroglycan C;
- repeated cocaine;
Addiction to psychostimulants elicits behavioral and biochemical changes that are assumed to be mediated by alterations of gene expression in the brain. The changes in gene expression after 3 weeks of withdrawal from chronic cocaine treatment were evaluated in the nucleus accumbens core and shell, dorsal prefrontal cortex and caudate using a complementary DNA (cDNA) array. The level of mRNA encoded by several genes was identified as being up- or down-regulated in repeated cocaine versus saline subjects. The results from the cDNA array were subsequently confirmed at the protein level with immunoblotting. Of particular interest, parallel up-regulation in protein and mRNA was found for the adenosine A1 receptor in the accumbens core, neuroglycan C in the accumbens shell, and the GluR5 glutamate receptor subtype in dorsal prefrontal cortex. However, there was an increase in TrkB protein in the nucleus accumbens core of cocaine-treated rats without a corresponding alteration in mRNA. These changes of gene expression in corticolimbic circuitry may contribute to the psychostimulant-induced behavioral changes associated with addiction.