Dopamine D1 Receptor Signaling System Regulates Ryanodine Receptor Expression in Ethanol Physical Dependence
Article first published online: 20 DEC 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 5, pages 771–783, May 2013
How to Cite
Kurokawa, K., Mizuno, K. and Ohkuma, S. (2013), Dopamine D1 Receptor Signaling System Regulates Ryanodine Receptor Expression in Ethanol Physical Dependence. Alcoholism: Clinical and Experimental Research, 37: 771–783. doi: 10.1111/acer.12036
- Issue published online: 24 APR 2013
- Article first published online: 20 DEC 2012
- Manuscript Accepted: 15 SEP 2012
- Manuscript Received: 6 FEB 2012
- Ministry of Health, Labor, and Welfare
- Kawasaki Medical University. Grant Numbers: 22-A25, 23B-28
- Physical Dependence;
- Ryanodine Receptors;
- Dopamine D1 Receptors
Ryanodine receptors (RyRs) amplifying activity-dependent calcium influx via calcium-induced calcium release play an important role in central nervous system functions including learning, memory, and drug abuse. In this study, we investigated the role and the regulatory mechanisms of RyR expression under continuous exposure of mice to ethanol (EtOH) vapor for 9 days.
The model of EtOH physical dependence was prepared as follows: 8-week-old male ddY mice were exposed to EtOH vapor for 9 days. Protein and mRNA of RyR-1, RyR-2, and RyR-3 in the frontal cortex and limbic forebrain were determined by Western blot and real-time RT-PCR analysis, respectively.
Exposure of mice to EtOH vapor for 9 days induced significant withdrawal signs when estimated with withdrawal score, which was dose-dependently suppressed by intracerebroventricular administration of dantrolene, an RyR antagonist. Protein levels of RyR-1 and RyR-2 in the frontal cortex and limbic forebrain significantly increased during EtOH vapor exposure for 9 days with increased expression of their mRNA, whereas that of RyR-3 in these 2 brain regions showed no changes. Increased proteins and mRNA of RyR-1 and RyR-2 were completely abolished by SCH23390, a selective antagonist of dopamine D1 receptors (D1DRs), but not by sulpiride, a selective antagonist of D2DRs.
RyRs play a critical role in the development of EtOH physical dependence and that the up-regulation of RyRs in the brain of mouse, showing EtOH physical dependence is regulated by D1DRs.