• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Addiction biology >The mGluR5 antagonist MPEP elevates accumbal dopamine and glycine levels; interaction with strychnine-sensitive glycine receptors.
【24h】

The mGluR5 antagonist MPEP elevates accumbal dopamine and glycine levels; interaction with strychnine-sensitive glycine receptors.

机译：mGluR5拮抗剂MPEP可提高多巴胺和甘氨酸的累积水平;与苯丙氨酸敏感性甘氨酸受体的相互作用。

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

Studies have indicated that the metabotropic glutamate receptor 5 (mGluR5) antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) decreases ethanol self-administration, and the same receptor type was also suggested to be involved in the mechanism of action of the anti-craving substance acamprosate. Our previous research suggested that glycine receptors (GlyRs) in the nucleus accumbens (nAc) play a major part in mediating the dopamine-elevating properties of ethanol and are highly involved in the ethanol intake-reducing effect of acamprosate. The aim of this study was to examine if modulation of nAc dopamine via mGluR5 antagonism or GlyR agonism is a linked or separated phenomena. The extracellular levels of dopamine as well as of the GlyR ligands, glycine, taurine and beta-alanine were measured in the nAc by means of microdialysis after local perfusion of MPEP (100 or 500 microM) with or without pre-treatment with strychnine. MPEP increased dopamine levels, an effect that was blocked by pre-treatment with strychnine. In addition, the higher MPEP concentration increased glycine output, whereas no alterations of taurine or beta-alanine were observed. These results indicate a relationship between the glutamatergic and glycinergic transmitter systems in regulating dopamine output, possibly via alteration of extracellular glycine levels. Taken together with our previous data demonstrating the importance of accumbal GlyRs both in ethanol-induced elevation of nAc dopamine and in ethanol consumption, it is plausible that the effects of MPEP treatment, on dopamine output and on ethanol intake, may be mediated via interaction with the same neuronal circuitry that previously has been demonstrated for ethanol, taurine and acamprosate.
机译：研究表明，代谢型谷氨酸受体5（mGluR5）拮抗剂6-甲基-2-（苯基乙炔基）-吡啶（MPEP）减少了乙醇的自我给药，并且还建议使用相同的受体类型参与该药物的作用机制。抗渴望物质阿坎酸。我们以前的研究表明伏隔核（nAc）中的甘氨酸受体（GlyRs）在介导乙醇的多巴胺升高特性中起主要作用，并且与阿坎酸的乙醇摄入减少作用高度相关。这项研究的目的是检查通过mGluR5拮抗作用或GlyR激动作用对nAc多巴胺的调节是连锁还是分开的现象。在局部灌注MPEP（100或500 microM）（有或没有用士的碱）的情况下，通过微渗析法在nAc中测量多巴胺以及GlyR配体，甘氨酸，牛磺酸和β-丙氨酸的细胞外水平。 MPEP增加了多巴胺水平，该作用被士的宁进行了预处理。此外，较高的MPEP浓度可增加甘氨酸产量，而未观察到牛磺酸或β-丙氨酸的变化。这些结果表明谷氨酸能和甘氨酸能递质系统之间可能通过改变细胞外甘氨酸水平来调节多巴胺输出。结合我们先前的数据表明，GlyRs在乙醇引起的nAc多巴胺升高和乙醇消耗中的重要性，可以认为MPEP治疗对多巴胺输出和乙醇摄入的影响可能是通过与与以前针对乙醇，牛磺酸和阿坎酸所证明的神经回路相同。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
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