Present address: Center for Molecular and Behavioral Neuroscience, Rutgers State University, Newark, NJ 07102, USA.
Long-lasting dysregulation of gene expression in corticostriatal circuits after repeated cocaine treatment in adult rats: effects on zif 268 and homer 1a
Article first published online: 8 APR 2009
© The Authors (2009). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 29, Issue 8, pages 1615–1626, April 2009
How to Cite
Unal, C. T., Beverley, J. A., Willuhn, I. and Steiner, H. (2009), Long-lasting dysregulation of gene expression in corticostriatal circuits after repeated cocaine treatment in adult rats: effects on zif 268 and homer 1a. European Journal of Neuroscience, 29: 1615–1626. doi: 10.1111/j.1460-9568.2009.06691.x
- Issue published online: 14 APR 2009
- Article first published online: 8 APR 2009
- Received 9 December 2008, revised 27 January 2009, accepted 2 February 2009
- immediate-early gene;
Human imaging studies show that psychostimulants such as cocaine produce functional changes in several areas of cortex and striatum. These may reflect neuronal changes related to addiction. We employed gene markers (zif 268 and homer 1a) that offer a high anatomical resolution to map cocaine-induced changes in 22 cortical areas and 23 functionally related striatal sectors, in order to determine the corticostriatal circuits altered by repeated cocaine exposure (25 mg/kg, 5 days). Effects were investigated 1 day and 21 days after repeated treatment to assess their longevity. Repeated cocaine treatment increased basal expression of zif 268 predominantly in sensorimotor areas of the cortex. This effect endured for 3 weeks in some areas. These changes were accompanied by attenuated gene induction by a cocaine challenge. In the insular cortex, the cocaine challenge produced a decrease in zif 268 expression after the 21-day, but not 1-day, withdrawal period. In the striatum, cocaine also affected mostly sensorimotor sectors. Repeated cocaine resulted in blunted inducibility of both zif 268 and homer 1a, changes that were still very robust 3 weeks later. Thus, our findings demonstrate that cocaine produces robust and long-lasting changes in gene regulation predominantly in sensorimotor corticostriatal circuits. These neuronal changes were associated with behavioral stereotypies, which are thought to reflect dysfunction in sensorimotor corticostriatal circuits. Future studies will have to elucidate the role of such neuronal changes in psychostimulant addiction.