Intracellular calcium chelation with BAPTA-AM modulates ethanol-induced behavioral effects in mice
Intracellular calcium chelation with BAPTA-AM modulates ethanol-induced behavioral effects in mice
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DOI：
10.1016/j.expneurol.2012.01.016
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发表时间：
2012-04-01
影响因子：
5.3
通讯作者：
Aragon, Carlos M. G.
中科院分区：
文献类型：
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作者：
Balino, Pablo;Monferrer, Lidon;Aragon, Carlos M. G.
钙 (Ca2+) 被认为是最普遍、最通用和最通用的细胞内信号分子之一，负责控制众多细胞过程。乙醇对 Ca2+ 分布和通量的影响已在体外得到广泛研究，表明急性乙醇给药可以以剂量依赖性方式调节细胞内 Ca2+ 浓度。在体内，Ca2+ 操纵与相应的乙醇诱导的行为效应之间的关系主要集中在通过电压门控 Ca2+ 通道的 Ca2+ 通量。本研究调查了内向 Ca2+ 电流在乙醇引起的精神运动效应（刺激和镇静）和乙醇摄入中的作用。我们研究了快速 Ca2+ 螯合剂 BAPTA-AM 对乙醇诱导的运动活性的影响以及乙醇的镇静作用。 Swiss (RjOrl) 小鼠在乙醇 (0-4 g/kg) 攻击前 30 分钟用 BAPTA-AM (0-10 mg/kg) 预处理。我们的结果表明，BAPTA-AM 预处理可防止乙醇产生的运动刺激，而不改变基础运动。相比之下，BAPTA-AM 逆转了乙醇诱导的催眠作用。在第二组实验中，我们研究了细胞内 Ca2+ 螯合对乙醇摄入的影响。按照黑暗中饮用的方法，向雄性 C57BL/6J 小鼠提供 20% v/v 乙醇、自来水或 0.1% 甜水。这些实验的结果表明，BAPTA-AM 预处理（0-5 mg/kg）以剂量依赖性方式减少乙醇消耗，同时水和甜水摄入量不受影响。我们的研究结果支持内向 Ca2+ 电流在介导乙醇诱导的不同行为反应中的作用。我们的结果与表明乙醇似乎比其他精神活性药物对细胞内 Ca2+ 操作更敏感的数据一起讨论。 (C) 2012 Elsevier Inc. 保留所有权利。
Calcium (Ca2+) has been characterized as one of the most ubiquitous, universal and versatile intracellular signaling molecules responsible for controlling numerous cellular processes. Ethanol-induced effects on Ca2+ distribution and flux have been widely studied in vitro, showing that acute ethanol administration can modulate intracellular Ca2+ concentrations in a dose dependent manner. In vivo, the relationship between Ca2+ manipulation and the corresponding ethanol-induced behavioral effects have focused on Ca2+ flux through voltage-gated Ca2+ channels. The present study investigated the role of inward Ca2+ currents in ethanol-induced psychomotor effects (stimulation and sedation) and ethanol intake. We studied the effects of the fast Ca2+ chelator, BAPTA-AM, on ethanol-induced locomotor activity and the sedative effects of ethanol. Swiss (RjOrl) mice were pretreated with BAPTA-AM (0-10 mg/kg) 30 min before an ethanol (0-4 g/kg) challenge. Our results revealed that pretreatment with BAPTA-AM prevented locomotor stimulation produced by ethanol without altering basal locomotion. In contrast, BAPTA-AM reversed ethanol-induced hypnotic effects. In a second set of experiments, we investigated the effects of intracellular Ca2+ chelation on ethanol intake. Following a drinking-in-the-dark methodology, male C57BL/6J mice were offered 20% v/v ethanol, tap water, or 0.1% sweetened water. The results of these experiments revealed that BAPTA-AM pretreatment (0-5 mg/kg) reduced ethanol consumption in a dose-dependent manner while leaving water and sweetened water intake unaffected. Our findings support the role of inward Ca2+ currents in mediating different behavioral responses induced by ethanol. Our results are discussed together with data indicating that ethanol appears to be more sensitive to intracellular Ca2+ manipulations than other psychoactive drugs. (C) 2012 Elsevier Inc. All rights reserved.