Specific involvement of neurotensin type 1 receptor in the neurotensin-mediated in vivo dopamine efflux using knock-out mice
Specific involvement of neurotensin type 1 receptor in the neurotensin-mediated in vivo dopamine efflux using knock-out mice
复制标题
DOI：
10.1046/j.1471-4159.2003.02231.x
复制
发表时间：
2004-04-01
影响因子：
4.7
通讯作者：
Suaud-Chagny, MF
中科院分区：
文献类型：
--
作者：
Leonetti, M;Brun, P;Suaud-Chagny, MF
神经紧张素是一种三肽神经递质，已知与精神疾病、各种生理过程和几种不同的神经生物学机制有关，包括调节伏核多巴胺释放。从大鼠脑中克隆出两个神经紧张素细胞外结合位点，即NT1-和nt2受体（NT1R和NT2R）。这些受体因其不同的体外药理学性质而可区分，但现有的药理学工具在体内的效力和特异性较弱。基因工程敲除小鼠的使用为研究它们各自的作用提供了一个强有力的替代经典药理学方法。在这项研究中，使用体内差分脉冲安培法，我们表明，在野生型小鼠中，神经紧张素应用于腹侧被盖区剂量依赖性地唤起伏隔核中的多巴胺外排。这种神经紧张素介导的外排在缺乏NT1R的小鼠中显著减少，而在nt2r缺失的小鼠中则不受影响。这一发现表明，神经紧张素在野生型小鼠伏隔核诱发的多巴胺外排有很大一部分是通过存在于腹侧被盖区的NT1R介导的。
Neurotensin is a tridecapeptide neurotransmitter known to be involved in psychiatric disorders, various physiological processes and several different neurobiological mechanisms, including modulation of accumbal dopamine release. Two neurotensin extracellular binding sites, namely NT1- and NT2-receptor (NT1R and NT2R), have been cloned from the rat brain. These receptors are distinguishable by their different in vitro pharmacological properties but the available pharmacological tools have weak in vivo potency and specificity. The use of genetically engineered knock-out mice has provided a powerful alternative to the classical pharmacological approach to investigate their respective roles. In this study, using in vivo differential pulse amperometry, we show that, in wild-type mice, neurotensin application into the ventral tegmental area dose-dependently evokes dopamine efflux in the nucleus accumbens. This neurotensin-mediated efflux is dramatically decreased in mice lacking NT1R while it is unaffected in NT2R-deleted mice. This finding indicates that a large part of the dopamine efflux evoked by neurotensin in the nucleus accumbens of wild-type mice is mediated via NT1R present in the ventral tegmental area.