The epigenetic effect of nicotine on dopamine D1 receptor expression in rat prefrontal cortex
Article first published online: 27 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 67, Issue 9, pages 545–552, September 2013
How to Cite
Gozen, O., Balkan, B., Yildirim, E., Koylu, E. O. and Pogun, S. (2013), The epigenetic effect of nicotine on dopamine D1 receptor expression in rat prefrontal cortex. Synapse, 67: 545–552. doi: 10.1002/syn.21659
- Issue published online: 17 JUL 2013
- Article first published online: 27 MAR 2013
- Accepted manuscript online: 28 FEB 2013 06:10AM EST
- Manuscript Accepted: 22 FEB 2013
- Manuscript Received: 14 DEC 2012
- Ege University Research Fund Grant . Grant Number: 2010-BAUM-001
- histone acetylation;
- prefrontal cortex;
Nicotine is a highly addictive drug and exerts its effect partially through causing dopamine release, thereby increasing intrasynaptic dopamine levels in the brain reward systems. Dopaine D1 receptor (DRD1) mRNAs and receptors are localized in reward-related brain regions, which receive cholinergic input. The aim of this study is to evaluate whether nicotine administration affects the expression of DRD1s, and if so, whether epigenetic mechanisms, such as histone acetylation, are involved. Twenty Male Sprague Dawley rats received nicotine (0.4 mg/kg/day, s.c.) or saline injections for 15 days. After nicotine/saline treatment, rats were perfused with saline; prefrontal cortex (PFC), corpus striatum (STR), and ventral tegmental area (VTA) were dissected. Homogenates were divided into two parts for total RNA isolation and histone H4 acetylation studies. DRD1 mRNA expression was significantly higher in the PFC of the nicotine-treated group compared with controls; similar trends were observed in the VTA and STR. To study epigenetic regulation, the 2kb upstream region of the DRD1 gene promoter was investigated for histone H4 acetylation in PFC samples. After chromatin immunoprecipitation with anti-acetyl histone H4 antibody, we found an increase in histone acetylation by two different primer pairs which amplified the −1365 to −1202 (P < 0.005) and −170 to +12 (P < 0.05) upstream regions of the DRD1 promoter. Our results suggest that intermittent subcutaneous nicotine administration increases the expression of DRD1 mRNA in the PFC of rats, and this increase may be due to changes in histone H4 acetylation of the 2kb promoter of the DRD1 gene. Synapse 67:545–552, 2013. © 2013 Wiley Periodicals, Inc.