Tissue levels and in vivo release of tachykinins and GABA in striatum and substantia nigra of rat brain after unilateral striatal dopamine denervation

Tissue levels and in vivo release of tachykinins and GABA in striatum and substantia nigra of rat brain after unilateral striatal dopamine denervation
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单侧纹状体多巴胺去神经后大鼠脑纹状体和黑质中速激肽和 GABA 的组织水平和体内释放

DOI:
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发表时间:
2004
影响因子:
2
通讯作者:
Urban Ungerstedt
Urban Ungerstedt
中科院分区:
医学4区
文献类型:
--
作者:
Nils Lindefors;Ernst Brodin;U. Tossman;J. Segovia;Urban Ungerstedt

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本研究测定了单侧6-羟多巴胺损毁大鼠黑质-纹状体多巴胺通路后,双侧纹状体和黑质中P物质(SP)、神经激肽A(NKA)和GABA的脑组织水平和体内释放。假注射动物作为对照。多巴胺去神经支配使损伤同侧纹状体(-38%)和损伤同侧(-54%)和对侧(-38%)黑质中的SP组织水平降低。NKA在纹状体中没有显著变化,但在病变同侧(-50%)和对侧(-40%)的黑质中降低(与SP一样)。GABA组织水平在失神经纹状体中增加(+20%),在两侧的黑质中保持不变。SP,NKA和GABA的细胞外水平测定与微透析在体内基础条件下,并在刺激与钾通过微透析探针局部管理。与假手术动物相比,病变同侧黑质中SP和NKA的刺激释放分别减少了39%和64%,而纹状体中SP或NKA释放没有变化。纹状体中GABA的基础释放增加了296%和76%,在多巴胺去神经纹状体的刺激过程中,而在黑质中检测到GABA的基础或刺激释放没有变化。我们认为,增加GABA释放多巴胺失神经纹状体可能是由于减少多巴胺介导的抑制当地GABA神经元。此外,减少黑质释放的SP和NKA同侧的病变建议引起的增加GABA抑制纹状体的SP和NKA含有纹状体黑质神经元。
SummaryBrain tissue levels and in vivo release of substance P (SP) and neurokinin A (NKA) and GABA were measured bilaterally in striatum and substantia nigra of the rat, after a unilateral 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway. Sham injected animals served as controls. The dopamine denervation decreased the tissue levels of SP in striatum (-38%) ipsilateral to the lesion and in substantia nigra both ipsi- (-54%) and contralateral (-38%) to the lesion. NKA was not significantly changed in the striatum, but decreased (like SP) in the substantia nigra both ipsi- (-50%) and contralateral (-40%) to the lesion. GABA tissue levels increased in the denervated striatum (+20%) and remained unchanged in substantia nigra at both sides. The extracellular levels of SP, NKA and GABA were measured with microdialysis in vivo at basal conditions and during stimulation with potassium administered locally via the microdialysis probe. The stimulated release of SP and NKA in the substantia nigra ipsilateral to the lesion was compared to in sham operated animals reduced with 39% and 64%, respectively, while no change in SP or NKA release was detected in the striatum. The basal release of GABA in the striatum was increased with 296% and with 76% during stimulation in the dopamine denervated striatum, while no change in GABA basal or stimulated release was detected in the substantia nigra. We suggest that the increased GABA release in the dopamine denervated striatum may be due to a decreased dopamine mediated inhibition of local GABA neurons. Furthermore, the decreased nigral release of SP and NKA ipsilateral to the lesion is suggested to be caused by an increased GABA inhibition in striatum of SP- and NKA-containing striato-nigral neurons.
多巴胺拮抗剂氟哌啶醇可降低大鼠纹状体黑质神经元中 P 物质、K 物质和前速激肽 mRNA。
DOI: --
发表时间: 1986
期刊: The Journal of biological chemistry
影响因子: --
作者:
Bannon,MJ;Lee,JM;Giraud,P;Young,A;Affolter,HU;Bonner,TI
通讯作者: Bonner,TI