[Mechanisms of ethanol-induced type I IP3 receptor expression]

Ethanol has a variety of action on neuronal functions, though its mechanism of action remains uncertain. Previous investigations have demonstrated functional alteration of neurotransmitter receptors and ion channels by ethanol at its concentration observed in the blood of alcoholics. Our recent studies have shown that chronic ethanol treatment up-regulates high voltage-gated L-type calcium channels and ryanodine receptors, both of which regulate intracellular Ca2+ concentration, and that the up-regulation of these calcium channels participates in behavioral changes including the rewarding effect. Among inositol 1,4,5-trisphosphate receptors (IP3Rs) classified into three different subtypes (type 1 (IP3R-1), type 2, and type 3 IP3Rs) with distinct physiological properties, IP3R-1 is the major neuronal member in the central nervous system, predominantly enriched in cerebellar Purkinje cells and abundant in neurons in the cerebral cortex. Although the most important result of IP3R channel functions is the change in intracellular Ca2+ concentration and phosphorylation of IP3Rs, there are few available data on ethanol effect on IP3Rs. In this report, we demonstrate the functional relationship between ethanol-induced rewarding effect and IP3R-1 expression and regulatory mechanisms of IP3R-1 expression after chronic ethanol exposure, especially focusing on Ca(2+)-related signal transduction pathways via dopamine D1 receptors using mouse cerebral cortical neurons.