[Role of intracellular Ca2+ dynamics in the development of drug dependence--Participation of Inositol 1,4,5-trisphosphate receptors].

Abstract

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are classified to a multigene family of channel proteins that mediate Ca2+ release from endoplasmic reticulum, and are one of regulators to modify intracellular Ca2+ concentration. Little is known about functional relationship between rewarding effects due to drugs of abuse and IP3Rs. This report reviews the roles and regulatory mechanisms of intracellular Ca2+ channels, especially type 1 IP3Rs (IP3Rs-1), in brain of animals with rewarding effects produced by drugs of abuse. Our recent studies have reported that the blockade of IP3Rs suppresses the development of rewarding effects on methamphetamine or cocaine, suggesting that functional up-regulation of IP3R-1 occurs during the development of rewarding effects. Moreover, the critical expression of IP3R-1 in the development of methamphetamine- and cocaine-induced rewarding effects are regulated by Ca2+ participating in signal transduction pathways via both dopamine D1 and D2 receptors. Taken together these results it is suggested that the changes in IP3R-1 play an essential role in the development of drug dependence.