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首页> 外文期刊>The European Journal of Neuroscience >Blockade of neurotensin receptors suppresses the dopamine D1/D2 synergism on immediate early gene expression in the rat brain.
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Blockade of neurotensin receptors suppresses the dopamine D1/D2 synergism on immediate early gene expression in the rat brain.

机译：神经降压素受体的阻滞抑制大鼠脑中立即早期基因表达上的多巴胺D1 / D2协同作用。

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摘要

A remarkable feature of dopamine functioning is that the concomitant activation of D1-like and D2-like receptors acts to intensify the expression of various dopamine-dependent effects, in particular the expression of the immediate-early genes, c-fos and zif268. Using non-peptide neurotensin receptor antagonists, including SR48692, we have determined that blockade of neurotensin receptors reduced the cooperative responses of direct acting D2-like (quinpirole) and partial D1-like (SKF38393) dopamine agonists on the expression of Fos-like antigens and zif268 mRNA. Pretreatment with SR48692 (3 and 10 mg/kg) reduced the number of Fos-like immunoreactive cells produced by the combined administration of SKF38393 (20 mg/kg) and quinpirole (1 mg/kg) in the caudate-putamen, nucleus accumbens, globus pallidus and ventral pallidum. High-affinity neurotensin receptors are likely to be involved in these D1-like/D2-like cooperative responses, as compounds structurally related to SR48692, SR48527 (3 mg/kg) and its (-)antipode, SR49711 (3 mg/kg), exerted a stereospecific antagonism in all selected brain regions. Pretreatment with SR48692 (10 mg/kg) also diminished Fos induction by the indirect dopamine agonist, cocaine (25 mg/kg), particularly at the rostral level of the caudate-putamen. In situ hybridization experiments in the caudate-putamen indicated that SR48692 (10 mg/kg) markedly reduced zif268 mRNA labelling produced by SKF38393 plus quinpirole in cells not expressing enkephalin mRNA, but was unable to affect the concomitant decrease of zif268 mRNA labelling in enkephalin-positive cells. Taken together, the results of the present study indicate that neurotensin is a key element for the occurrence of cooperative responses of D2-like and partial D1-like agonists on immediate-early gene expression.
机译：多巴胺功能的显着特征是D1样和D2样受体的伴随活化可增强各种多巴胺依赖性效应的表达，特别是立即早期基因c-fos和zif268的表达。使用包括SR48692在内的非肽类神经降压素受体拮抗剂，我们已经确定，对神经降压素受体的阻断降低了直接作用的D2样（喹吡罗）和部分D1样（SKF38393）多巴胺激动剂对Fos样抗原表达的协同反应。和zif268 mRNA。用SR48692（3和10 mg / kg）预处理可减少在尾状丘脑，伏隔核中联合施用SKF38393（20 mg / kg）和喹吡罗（1 mg / kg）产生的Fos样免疫反应细胞的数量，苍白球和腹侧苍白球。高亲和性神经降压素受体可能与这些D1样/ D2样的协同反应有关，因为与SR48692，SR48527（3 mg / kg）及其正负电极SR49711（3 mg / kg）结构相关，在所有选定的大脑区域发挥了立体定向拮抗作用。用SR48692（10 mg / kg）预处理还减少了间接多巴胺激动剂可卡因（25 mg / kg）的Fos诱导作用，尤其是在尾状-丘脑的鸟嘴角处。在尾状-足状核中的原位杂交实验表明，SR48692（10 mg / kg）在不表达脑啡肽mRNA的细胞中显着降低了SKF38393加喹吡罗产生的zif268 mRNA标记，但无法影响脑啡肽-z伴随zif268 mRNA标记的减少阳性细胞。两者合计，本研究的结果表明，神经降压素是D2样和部分D1样激动剂对立即早期基因表达发生协同反应的关键因素。

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