Although Type 1 inositol 1,4,5-trisphosphate receptors (IP3Rs-1) are one of the major calcium channels to regulate intracellular Ca2+ concentration, there have been few available data how their expression is modified by long-term exposure to ethanol. The present study attempted to clarify mechanisms of modification of IP3R-1 expression during long-term ethanol exposure by γ-aminobutyric acid (GABA)A receptors using mouse cerebral cortical neurons. Long-term exposure to ethanol induced IP3R-1 protein upregulation following increased expression of its mRNA. Pretreatment with muscimol, a selective GABAA receptor agonist, significantly suppressed the ethanol-induced upregulation of IP3R-1 protein and its mRNA, which was significantly abolished by bicuculline, a selective GABAA receptor antagonist. These results indicate that GABAA receptors negatively regulate the ethanol-induced upregulation of IP3R-1 protein expression via the suppression of gene transcription. Synapse, 2013. © 2012 Wiley Periodicals, Inc.