title: Dopamine D1 receptor signaling system regulates ryanodine receptor expression in ethanol physical dependence.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Koji
authors.initials: K
authors.lastname: Mizuno
authors.forename: Seitaro
authors.initials: S
authors.lastname: Ohkuma
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003620:Dantrolene / Q000494:pharmacology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005625:Frontal Lobe / Q000378:metabolism; D008297:Male; D051379:Mice; D016548:Prosencephalon / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D002492:Central Nervous System Depressants; C583261:Drd1 protein, mouse; D017447:Receptors, Dopamine D1; D019837:Ryanodine Receptor Calcium Release Channel; C534628:SCH 23390; D000431:Ethanol; D003620:Dantrolene