药物成瘾伴随中枢神经系统内钙离子通道数目及开放状态的适应性改变.大量证据表明,L型电压依赖性钙通道（LTCCs）可通过调节神经递质的释放、神经兴奋性、基因的转录及突触可塑性等过程调控成瘾行为.最新的研究还表明,LTCCs的不同亚型Ca_v1.2和Ca_v1.3对药物成瘾的调控分别依赖于D1及D2受体,且具有脑区及分子机制特异性.并且,Cav1.3的a亚基能够与内质网钙通道蛋白（Ry R2）的N末端氨基酸相互结合,促进胞内钙库Ca^2＋的释放.此外,骨架蛋白激酶A锚定蛋白79/150（AKAP79/150）可将LTCCs锚定在突触膜上,从而调控成瘾药物诱导的突触可塑性改变.本文将重点讨论LTCCs在药物成瘾中发挥的调控作用及其潜在的细胞及分子机制.

Changes of intracellular calcium are the fundament of cell physiological function and the key factor in intracellular signal transduction and gene expression. Recently more studies have been focusing on the relationship between voltage dependent calcium channels（VDCCs） and drug addiction. A great deal of evidence suggests that L-type VDCCs（LTCCs）, which are activated by membrane depolarization, play an important role in drug addiction by affecting the release of neurotransmitters, excitability of neurons, gene transcription and synaptic plasticity. LTCCs are divided into four subtypes： Ca_v1.1, Ca_v1.2, Ca_v1.3 and Ca_v1.4, according to the conduction of single channel and sensitivity to calcium antagonists and agonists. Among them Cav1.2 and Ca_v1.3 are mainly expressed in the central nervous system. It is reported that the increasing of intracellular calcium induced by LTCCs is crucial in physical dependence and withdrawal symptoms of addictive drugs such as morphine. In addition, the enhancement of c AMP-response element binding protein（CREB） and ryanodine receptor 2（Ry R2） induced by LTCCs on endoplasmic reticulum（ER） stimulate the release of calcium in cytoplasm, leading to a long-term increase in intracellular calcium. This relation might underlie the dependence and tolerance of nicotine. Moreover, it is reported that LTCCs also take part in nonsomatic signs of drug withdrawal. For example, intraperitoneal injection of LTCCs antagonists can reduce nonsomatic withdrawal symptoms in chronic nicotine-dependent rats, like anxiety, memory impartment and depression-like effects. Furthermore, recent researches also find that Ca_v1.2 and Ca_v1.3 play an important role in the acquisition and expression of cocaine-induced behavioral sensitization through different molecular mechanisms in specific brain regions. For instance, Cav_1.3 in the ventral tegmental area（VTA） affects the development of cocaine sensitization by activating extracellular regulated protein kinases 2（ERK2）; While in the expression of cocaine sensitization, on the one hand, Ca_v1.2 opening in the nucleus accumbens（NAc） regulated by dopamine 1（D1） receptor, activates its downstream Ca~（2＋）/calmodulin-dependent protein kinase II（Ca MK II） and ERK2, leading to the phosphorylation at GluA1~（Ser831） of a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor（AMPAR） and the membrane insertion of AMPA receptor GluA 1 subunit. This process needs the activation of Ca_v1.3 in the VTA. On the other hand, activation of Ca_v1.3 in the dorsal striatum（DS）, which is regulated by D2 receptor, suppresses its downstream activation, including CREB, DARPP-32, Akt and GSK-3b, leading to the reduction of phosphorylation at GLuA1~（Ser845） and the expression level of membrane GluA1. Besides, LTCCs are also involved in the acquisition, expression and reinstatement of addiction memory. Recent studies indicate that LTCCs play different roles in different phases of addiction memory. For example, LTCCs in the VTA are involved in the acquisition of morphine conditioned place preference（CPP） by activating N-methyl-D-aspartate receptor（NMDAR）; Whereas LTCCs in the NAc regulate development and expression of morphine CPP via interacting with the Ry R2 which can induce the calcium release from the ER. Moreover, it has been demonstrated that the scaffold protein A-kinase anchor proteins79/150（AKAP79/150） can anchor LTCCs to synaptic membranes, which might be a potential mechanism underlying the reinstatement of addiction memory induced by drugs. Therefore, in this review, we will focus on summarizing the role and the potential cellular and molecular mechanisms of LTCCs in drug addiction, with the expectation of expanding the perspectives onto further exploration of the neurobiological mechanisms of addiction memory.