Kurokawa Kazuhiro, Mizuno Koji, Ohkuma Seitaro
Nihon Arukoru Yakubutsu Igakkai Zasshi. 2014 Jun;49(3):169-76.
Ca2+ influx into neuron through L-type voltage-gated Ca2+ channels (VDCCs) plays an important role in psychostimulant-induced behaviroal and neuronal plasticity. On the other hand, Ca2+ release from ryanodine receptors in the endoplasmic reticulum is one mechanism altering the intracellular Ca2+ concentration. Little is known about functional relationship between psychological dependence due to drugs of abuse and L-type VDCCs or ryanodine receptors. In this paper, we review the roles and regulatory mechanisms of intracellular Ca2+ channels, especially L-type VDCCs and ryanodine receptors in brain of animals with drug dependence. Our recent study have reported that blockade of L-type VDCCs inhibits the development of rewarding effects on drugs of abuse (methamphetamine, cocaine and morphine), suggesting that up-regulation of L-type VDCCs (alpha 1C and alpha 1D subunits) occurs during the development of psychological dependence. Moreover, the critical expression of type-1 and -2 ryanodine receptors in the development of methamphetamine- and cocaine-induced rewarding effects are regulated by dopamine D1 receptors. These results suggest that changes in intracellular Ca2+ dynamics play an essential role in the development of drug dependence.
钙离子通过L型电压门控钙离子通道（VDCCs）流入神经元，在精神兴奋剂诱导的行为和神经元可塑性中发挥重要作用。另一方面，内质网中兰尼碱受体释放钙离子是改变细胞内钙离子浓度的一种机制。关于药物滥用所致心理依赖与L型VDCCs或兰尼碱受体之间的功能关系，目前所知甚少。在本文中，我们综述了细胞内钙离子通道，尤其是L型VDCCs和兰尼碱受体在药物依赖动物大脑中的作用及调节机制。我们最近的研究报道，阻断L型VDCCs可抑制对滥用药物（甲基苯丙胺、可卡因和吗啡）的奖赏效应的产生，这表明在心理依赖形成过程中L型VDCCs（α1C和α1D亚基）上调。此外，1型和2型兰尼碱受体在甲基苯丙胺和可卡因诱导的奖赏效应形成过程中的关键表达受多巴胺D1受体调节。这些结果表明，细胞内钙离子动态变化在药物依赖形成过程中起重要作用。
