Area de Psicobiología, Universtitat Jaume I, Avda. Sos Baynat s/n, 12071 Castellón, Spain.
Behav Brain Res. 2010 Jun 19;209(2):196-204. doi: 10.1016/j.bbr.2010.01.036. Epub 2010 Feb 1.
Calcium flux through voltage gate calcium channels (VGCC) is involved in many neuronal processes such as membrane depolarization, gene expression, hormone secretion, and neurotransmitter release. Several studies have shown that either acute or chronic exposure to ethanol modifies calcium influx through high voltage activated channels. Of special relevance is the L-type VGCC. Pharmacological manipulation of L-type calcium channels affects ethanol intake, ethanol discrimination and manifestations of withdrawal syndrome. The present study investigates the role of L-type channels on the psychomotor effects (stimulation and sedation/ataxia) of ethanol by testing the effects of different L-type calcium channel blockers (CCB) on such behaviors. Mice were pretreated intraperitoneally with the CCB, diltiazem (0-40 mg/kg) or verapamil (0-30 mg/kg) 30 min before ethanol (0-3.5 g/kg). Locomotion was measured in an open field chamber for 20 min immediately after ethanol. The two CCB tested prevented locomotor stimulation, but not locomotor suppression produced by ethanol. Doses of the two CCB which reduced ethanol stimulation, did not alter spontaneous locomotion. The ataxic effects of ethanol (1.25 g/kg), measured with an accelerating rotarod task, were not affected by diltiazem (20mg/kg) or verapamil (15 mg/kg). In addition, our results indicated that ethanol is more sensitive to the antagonism of L-type calcium channels than other drugs with stimulant properties; doses of the two CCB that reduced ethanol stimulation did not reduce the psychomotor effects of amphetamine, caffeine or cocaine. In conclusion, these data provide further evidence of the important involvement of L-type calcium channels in the behavioral effects produced by ethanol.
钙通过电压门控钙通道（VGCC）的流动参与许多神经元过程，如膜去极化、基因表达、激素分泌和神经递质释放。多项研究表明，急性或慢性暴露于乙醇会改变通过高电压激活通道的钙内流。特别相关的是 L 型 VGCC。L 型钙通道的药理学操纵会影响乙醇的摄入、乙醇的辨别和戒断综合征的表现。本研究通过测试不同 L 型钙通道阻滞剂（CCB）对这些行为的影响，研究 L 型通道在乙醇的精神运动效应（刺激和镇静/共济失调）中的作用。在乙醇（0-3.5 g/kg）之前 30 分钟，通过腹膜内给予 CCB、地尔硫卓（0-40 mg/kg）或维拉帕米（0-30 mg/kg）预处理小鼠。乙醇后立即在开放场室中测量 20 分钟的运动。两种测试的 CCB 可预防乙醇引起的运动刺激，但不能预防运动抑制。减少乙醇刺激的两种 CCB 的剂量不会改变自发运动。用加速旋转棒任务测量的乙醇的共济失调作用（1.25 g/kg）不受地尔硫卓（20mg/kg）或维拉帕米（15mg/kg）的影响。此外，我们的结果表明，乙醇对 L 型钙通道的拮抗作用比其他具有刺激特性的药物更敏感；减少乙醇刺激的两种 CCB 的剂量不会减少安非他命、咖啡因或可卡因的精神运动效应。总之，这些数据进一步证明了 L 型钙通道在乙醇产生的行为效应中的重要作用。
