AbstractFor review there are little available data on regulatory mechanisms of ryanodine receptor (RyR) expression with cocaine treatment, though methamphetamine was reported to up‐regulate RyRs in mouse brain. This study attempted to investigate regulatory mechanisms of RyR expression using the cerebral cortical neurons in primary culture intermittently exposed to a psychostimulant, cocaine. Intermittent exposure to cocaine (10 μM) significantly enhanced RyR 1 and 2 proteins and their mRNA, but not RyR 3 expression in the neurons. These cocaine‐induced increases of RyR proteins and their mRNA were dose‐dependently blocked by a dopamine D1 receptor antagonist (SCH23390), but not by a dopamine D2 receptor antagonist (sulpiride). These results indicate a regulatory role of dopamine D1 receptors in RyR expression bycocaine. Synapse, 2011. © 2011 Wiley‐Liss, Inc.