Interactions between 3,4-methylenedioxymethamphetamine and σ1 receptors
Interactions between 3,4-methylenedioxymethamphetamine and σ1 receptors
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DOI：
10.1016/j.ejphar.2006.09.038
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发表时间：
2006-12-28
影响因子：
5
通讯作者：
Matsumoto, Rae R.
中科院分区：
文献类型：
--
作者：
Brammer, Matthew K.;Gilmore, Deborah L.;Matsumoto, Rae R.
甲基苯丙胺和3，4-亚甲二氧基甲基苯丙胺（MDMA）在结构上相似，对健康构成严重和日益严重的威胁。我们实验室的早期研究表明，甲基苯丙胺与σ受体相互作用，这些受体的拮抗作用可以减弱甲基苯丙胺诱导的运动刺激和神经毒性。然而，目前还没有研究表明α受体与MDMA之间的相互作用。因此，本研究的目的是确定是否a受体参与MDMA的作用。在研究的第一部分，进行竞争和饱和结合试验，以测量MDMA与σ受体的相互作用。受体结合试验表明，与sigma 2亚型相比，MDMA优先与sigma（1）亚型相互作用，并且这种相互作用以竞争方式发生。研究的第二部分集中于雄性瑞士韦伯斯特小鼠的行为测量，以确定选择性σ（1）受体拮抗剂BD 1063（1-[2-（3，4-二氯苯基）乙基]-4-甲基哌嗪，0-30 mg/kg，i. p.）能减弱MDMA（0-50 mg/kg，i. p.）的运动兴奋作用。单独使用BD 1063对自发活动没有影响，但剂量依赖性地减弱了MDMA的自发刺激作用，并使MDMA剂量反应曲线显著向右移动。总之，这些数据支持MDMA与sigma（1）受体相互作用的功能相关性，并表明这些受体参与MDMA的兴奋作用。(c)2006 Elsevier B. V.保留所有权利。
Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) are structurally similar and represent a serious and growing health threat. Earlier studies in our laboratory have shown that methamphetamime interacts with sigma receptors and that antagonism of these receptors can attenuate methamphetamine-induced locomotor stimulation and neurotoxicity. However, no research exists which characterizes the interaction between a receptors and MDMA. Therefore, the goal of the present study was to determine whether a receptors are involved in the actions of MDMA. In the first part of the study, competition and saturation binding assays were performed to measure the interaction of MDMA with sigma receptors. The receptor binding assays revealed that MDMA interacts preferentially with the sigma(1) subtype, as compared to the sigma 2 subtype, and that this interaction occurs in a competitive manner. The second part of the study focused on behavioral measurements in male, Swiss Webster mice to determine whether a selective sigma(1) receptor antagonist, BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine, 0-30 mg/kg, i.p.) could attenuate the locomotor stimulant actions of MDMA (0-50 mg/kg, i.p.). BD1063 alone had no effect on locomotor activity, but dose-dependently attenuated the locomotor stimulant effects of MDMA and produced a significant shift to the right in the MDMA dose response curve. Together, the data support the functional relevance of the interaction of MDMA with sigma(1) receptors, and suggest that these receptors are involved in the stimulant actions of MDMA. (c) 2006 Elsevier B.V. All rights reserved.