• 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 >Disruption of noradrenergic transmission and the behavioural response to a novel environment in NK1R-/- mice.
【24h】

Disruption of noradrenergic transmission and the behavioural response to a novel environment in NK1R-/- mice.

机译：NK1R-/-小鼠体内去甲肾上腺素能传递的中断和对新环境的行为反应。

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

The behaviour of neurokinin-1-receptor gene knockout (NK1R-/-) mice, which lack functional, substance P-preferring receptors, resembles that of NK1R+/+ mice treated with an antidepressant. Because all antidepressants increase central monoamine transmission, we have investigated whether noradrenergic transmission is increased in NK1R-/- mice and, if so, whether this could influence their behaviour. In anaesthetized subjects, the concentration of extracellular noradrenaline in NK1R-/- mice was two-fourfold greater than in NK1R+/+ mice. Systemic administration of the alpha2-adrenoceptor antagonist, 2-(2,3-dihydro-2-methoxy-1,4-benzodioxan-2-yl)-4,5-dihydro-1H-imidazoline (RX 821002), in anaesthetized or freely moving animals increased extracellular noradrenaline in NK1R+/+ mice only. This suggests that the function of alpha2a-autoreceptors, which modulate noradrenergic transmission, is impaired in NK1R-/- mice. Consistent with this, [35S]GTPgammaS binding to activated alpha2a-adrenoceptors was lower (-70%) in the locus coeruleus, but not the frontal cortex, of NK1R-/- mice compared with their NK1R+/+ counterparts. RX 821002-pretreatment, followed by retrodialysis of the noradrenaline reuptake inhibitor, desipramine, into the frontal cortex of anaesthetized mice increased extracellular noradrenaline to the same extent in the two genotypes. Western blots confirmed that there was no difference in the amount of noradrenaline transporter protein in NK1R-/- and NK1R+/+ mice. Finally, the effects of RX 821002 on certain behaviours in a light/dark exploration box were blunted in NK1R-/- mice, but there was no consistent effect on anxiety-like behaviour in the two genotypes. It is concluded that the greater basal efflux of noradrenaline in NK1R-/- mice is explained by increased transmitter release, coupled with desensitization of somatodendritic alpha2a-adrenoceptors. These changes could contribute to the difference in the behavioural phenotypes.
机译：缺少功能性P物质优先受体的神经激肽1受体基因敲除（NK1R-/-）小鼠的行为类似于用抗抑郁药治疗的NK1R + / +小鼠的行为。因为所有抗抑郁药都会增加中枢单胺传递，所以我们研究了NK1R-/-小鼠中去甲肾上腺素传递是否增加，如果这样，是否会影响其行为。在麻醉的受试者中，NK1R-/-小鼠的细胞外去甲肾上腺素浓度比NK1R + / +小鼠高出四倍。全身麻醉下全身给药α2-肾上腺素受体拮抗剂2-（2,3-二氢-2-甲氧基-1,4-苯并二恶烷-2-基）-4,5-二氢-1H-咪唑啉（RX 821002）自由活动的动物仅在NK1R + / +小鼠中增加细胞外去甲肾上腺素。这表明在NK1R-/-小鼠中，α2a-自动受体的功能被调节，该功能可调节去甲肾上腺素能传递。与此相一致的是，与NK1R + / +对应物相比，在NK1R-/-小鼠的蓝斑中，但不是额叶皮层[35S] GTPgammaS与活化的α2a-肾上腺素受体的结合较低（-70％）。 RX 821002-预处理，然后将去甲肾上腺素再摄取抑制剂地昔帕明逆渗析到麻醉小鼠的额叶皮层中，两种基因型的细胞外去甲肾上腺素水平均相同。 Western印迹证实在NK1R-/-和NK1R + / +小鼠中去甲肾上腺素转运蛋白的含量没有差异。最后，在NK1R-/-小鼠中，RX 821002对明暗探索盒中某些行为的影响减弱了，但是在两种基因型中对焦虑样行为没有一致的影响。结论是，NK1R-/-小鼠中去甲肾上腺素的更大基础外排可通过增加的递质释放以及体树突状α2a-肾上腺素受体的脱敏作用来解释。这些变化可能会导致行为表型的差异。

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