• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Characterization of interactions between phencyclidine and amphetamine in rodent prefrontal cortex and striatum: Implications in NMDA/glycine-site-mediated dopaminergic dysregulation and dopamine transporter function.
【24h】

Characterization of interactions between phencyclidine and amphetamine in rodent prefrontal cortex and striatum: Implications in NMDA/glycine-site-mediated dopaminergic dysregulation and dopamine transporter function.

机译：啮齿动物前额叶皮层和纹状体中苯环利定和苯丙胺之间相互作用的特征：在NMDA /甘氨酸位点介导的多巴胺能失调和多巴胺转运蛋白功能中的意义。

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

N-Methyl-d-aspartate (NMDA) antagonists induced behavioral and neurochemical changes in rodents that serve as animal models of schizophrenia. Chronic phencyclidine (PCP, 15mg/(kgday) for 3 weeks via Alzet osmotic pump) administration enhances the amphetamine (AMPH)-induced dopamine (DA) efflux in prefrontal cortex (PFC), similar to that observed in schizophrenia. NMDA/glycine-site agonists, such as glycine (GLY), administered via dietary supplementation, reverse the enhanced effect. The present study investigated mechanisms of glycine-induced reversal of PCP-induced stimulation of AMPH-induced DA release, using simultaneous measurement of DA and AMPH in brain microdialysate, as well as peripheral and tissue AMPH levels. PCP treatment, by itself, increased peripheral and central AMPH levels, presumably via interaction with hepatic enzymes (e.g. cytochrome P450 CYP2C11). GLY (16% diet) had no effect on peripheral AMPH levels in the presence of PCP. Nevertheless, GLY significantly reduced extracellular/tissue AMPH ratios in both PFC and striatum (STR), especially following PCP administration, suggesting a feedback mediated effect on the dopamine transporter. GLY also inhibited acute AMPH (5mg/kg)-induced DA release in PFC, but not STR. These findings suggest that GLY may modulate DA release in brain by producing feedback regulation of dopamine transporter function, possibly via potentiation of NMDA-stimulated GABA release and presynaptic GABAB receptor activation. The present studies also demonstrate pharmacokinetic interaction between AMPH and PCP, which may be of both clinical and research relevance.
机译：N-甲基-d-天冬氨酸（NMDA）拮抗剂在啮齿动物中诱导了行为和神经化学变化，它们是精神分裂症的动物模型。慢性苯环利定（PCP，15mg /（kgday）通过Alzet渗透泵给药3周）可增强苯丙胺（AMPH）诱导的前额叶皮层（PFC）中的多巴胺（DA）外排，与精神分裂症相似。通过膳食补充剂施用的NMDA /甘氨酸位点激动剂，例如甘氨酸（GLY），逆转了增强的作用。本研究调查了甘氨酸逆转PCP诱导的AMPH诱导的DA释放刺激的甘氨酸逆转的机制，同时测量了脑微透析液中DA和AMPH以及外周和组织中的AMPH水平。 PCP治疗本身会增加外周和中枢AMPH的水平，大概是通过与肝酶（例如细胞色素P450 CYP2C11）的相互作用。在有PCP的情况下，GLY（16％的饮食）对外周AMPH水平没有影响。然而，GLY显着降低了PFC和纹状体（STR）的细胞外/组织AMPH比率，尤其是在PCP给药后，提示了对多巴胺转运蛋白的反馈介导作用。 GLY还抑制PFC中急性AMPH（5mg / kg）诱导的DA释放，但不抑制STR。这些发现表明，GLY可能通过产生多巴胺转运蛋白功能的反馈调节来调节大脑中DA的释放，这可能是通过增强NMDA刺激的GABA释放和突触前GABAB受体激活来实现的。本研究还证明了AMPH和PCP之间的药代动力学相互作用，可能具有临床和研究意义。

著录项

相似文献

  • 外文文献
  • 中文文献
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