...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Endogenous 5-HT, released by MDMA through serotonin transporter- and secretory vesicle-dependent mechanisms, reduces hippocampal excitatory synaptic transmission by preferential activation of 5-HT1B receptors located on CA1 pyramidal neurons.
【24h】

Endogenous 5-HT, released by MDMA through serotonin transporter- and secretory vesicle-dependent mechanisms, reduces hippocampal excitatory synaptic transmission by preferential activation of 5-HT1B receptors located on CA1 pyramidal neurons.

机译：MDMA通过血清素转运蛋白和分泌性囊泡依赖性机制释放的内源性5-HT通过优先激活位于CA1锥体神经元上的5-HT1B受体来减少海马兴奋性突触传递。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A multitude of different serotonin (5-HT) receptor types are expressed in the hippocampus, but the identity of receptors actually mediating the physiological response to endogenous 5-HT has not been determined. We combined pharmacologically induced release of 5-HT with patch-clamp recordings on disinhibited rat CA1 minislices to determine effects of endogenous 5-HT on the excitability of pyramidal neurons and synaptic transmission among them. We found that application of 5-HT releasers, 3,4-methylenedioxy-methamphetamine (MDMA) or p-methylthioamphetamine, at concentrations ranging from 2 to 50 micro m, reduced the excitatory synaptic transmission between CA1 pyramidal neurons without altering their basal electrical properties. This effect of MDMA was blocked by the selective 5-HT1B antagonist GR 55562, was dependent on endogenous 5-HT content and was mediated by presynaptically located, pertussis-toxin sensitive mechanisms. We found no other MDMA effects in our preparation, which indicates that the release of endogenous 5-HT preferentially stimulates 5-HT1B receptors on CA1 pyramidal neurons. Therefore, 5-HT1B receptor activation may represent a predominant component of the physiological response to endogenous 5-HT in the CA1. The high sensitivity of the 5-HT1B receptor-mediated reduction of polysynaptic excitatory responses to the extracellular 5-HT level enabled us to study mechanisms of the 5-HT releasing action of MDMA. Block of the serotonin transporter (SERT) with citalopram slowed the time course and reduced overall 5-HT release by MDMA. Depletion of vesicular 5-HT, by inhibition of vesicular monoamine transporter type 2 with tetrabenazine prevented the release. Thus although the SERT reversal contributes, a direct vesicle-depleting action is essential for MDMA release of 5-HT.
机译：在海马中表达了多种不同的5-羟色胺（5-HT）受体类型，但尚未确定实际上介导对内源性5-HT的生理反应的受体的身份。我们结合药理学上诱导的5-HT释放与膜片钳记录在抑制的大鼠CA1小切片上，以确定内源性5-HT对锥体神经元兴奋性和突触传递的影响。我们发现应用5-HT释放剂，3,4-亚甲二氧基-甲基苯丙胺（MDMA）或对甲硫基苯丙胺，浓度范围为2至50微米，可减少CA1锥体神经元之间的兴奋性突触传递，而不会改变其基础电特性。 。 MDMA的这种作用被选择性5-HT1B拮抗剂GR 55562阻断，取决于内源性5-HT含量，并由突触前定位的百日咳毒素敏感机制介导。我们在制剂中未发现其他MDMA效应，这表明内源性5-HT的释放优先刺激了CA1锥体神经元上的5-HT1B受体。因此，5-HT1B受体激活可能代表了CA1中对内源5-HT的生理反应的主要组成部分。 5-HT1B受体介导的多突触兴奋性反应对细胞外5-HT水平降低的高敏感性使我们能够研究MDMA 5-HT释放作用的机制。用西酞普兰阻断5-羟色胺转运蛋白（SERT）可减慢时间进程，并减少MDMA释放的总5-HT。通过用丁苯那嗪抑制2型囊泡单胺转运蛋白耗尽了5-HT，从而阻止了其释放。因此，尽管SERT逆转起作用，但直接的囊泡消耗作用对于5-HT的MDMA释放至关重要。

著录项

相似文献

  • 外文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号