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L 型电压门控钙通道在心理依赖形成中的上调。

Upregulation of L-type Ca(v)1 channels in the development of psychological dependence.

机构信息

Department of Pharmacology, Kawasaki Medical School, Kurashiki 701-0192, Japan.

出版信息

Synapse. 2010 Jun;64(6):440-4. doi: 10.1002/syn.20745.

Abstract

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.

摘要

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。

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