Department of Pharmacology, Kawasaki Medical School, Kurashiki 701-0192, Japan.
Synapse. 2010 Jun;64(6):440-4. doi: 10.1002/syn.20745.
Although L-type voltage-dependent Ca2+ channels regulate activity-dependent processes including synaptic plasticity and synapse formation, there are few data on the changes of Ca(v)1 channel expression in psychological dependence. This study investigated the role of L-type Ca(v)1 channel expression in the brain of mouse that was psychologically dependent on methamphetamine (2 mg/kg, subcutaneous injection [s.c.]), cocaine (10 mg/kg, s.c.), and morphine (5 mg/kg, s.c.) with the conditioned place preference paradigm. Intracerebroventricular administration of nifedipine (3, 10, and 30 nmol/mouse) dose-dependently reduced the development of methamphetamine-, cocaine-, and morphine-induced rewarding effect. Under such conditions, protein levels of both Ca(v)1.2 and Ca(v)1.3 in the frontal cortex and the limbic forebrain were significantly increased on methamphetamine-, cocaine-, and morphine-induced psychologically dependent mice. These findings suggest that the upregulation of Ca(v)1.2 and Ca(v)1.3 participated in the development of psychological dependence.
尽管 L 型电压依赖性 Ca2+ 通道调节包括突触可塑性和突触形成在内的活动依赖性过程，但关于 Ca(v)1 通道表达在心理依赖中的变化的数据很少。本研究通过条件性位置偏爱范式，调查了 L 型 Ca(v)1 通道表达在对安非他命（2mg/kg，皮下注射[s.c.]）、可卡因（10mg/kg，s.c.）和吗啡（5mg/kg，s.c.）产生心理依赖的小鼠大脑中的作用。脑室内给予硝苯地平（3、10 和 30nmol/只小鼠）可剂量依赖性地减少安非他命、可卡因和吗啡诱导的奖赏效应的产生。在这种情况下，在前脑皮层和边缘前脑的 Ca(v)1.2 和 Ca(v)1.3 蛋白水平在安非他命、可卡因和吗啡诱导的心理依赖小鼠中显著增加。这些发现表明，Ca(v)1.2 和 Ca(v)1.3 的上调参与了心理依赖的发展。
