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Dopamine D 1 Receptor Signaling System Regulates Ryanodine Receptor Expression in Ethanol Physical Dependence
Author(s) -
Kurokawa Kazuhiro,
Mizuno Koji,
Ohkuma Seitaro
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12036
Subject(s) - ryanodine receptor , medicine , endocrinology , sulpiride , forebrain , chemistry , dopamine , antagonist , receptor , dantrolene , calcium channel , hippocampus , calcium , biology , central nervous system
Background Ryanodine receptors ( R y R s) 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 R y R expression under continuous exposure of mice to ethanol ( E t OH ) vapor for 9 days. Methods The model of E t OH physical dependence was prepared as follows: 8‐week‐old male dd Y mice were exposed to E t OH vapor for 9 days. Protein and m RNA of R y R ‐1, R y R ‐2, and R y R ‐3 in the frontal cortex and limbic forebrain were determined by Western blot and real‐time RT ‐ PCR analysis, respectively. Results Exposure of mice to E t OH vapor for 9 days induced significant withdrawal signs when estimated with withdrawal score, which was dose‐dependently suppressed by intracerebroventricular administration of dantrolene, an R y R antagonist. Protein levels of R y R ‐1 and R y R ‐2 in the frontal cortex and limbic forebrain significantly increased during E t OH vapor exposure for 9 days with increased expression of their m RNA , whereas that of R y R ‐3 in these 2 brain regions showed no changes. Increased proteins and m RNA of R y R ‐1 and R y R ‐2 were completely abolished by SCH 23390, a selective antagonist of dopamine D 1 receptors ( D 1 DR s), but not by sulpiride, a selective antagonist of D2DRs . Conclusions RyRs play a critical role in the development of E t OH physical dependence and that the up‐regulation of R y R s in the brain of mouse, showing E t OH physical dependence is regulated by D 1 DR s.