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多次给予氟哌啶醇后大鼠尾状核-壳核神经元亚群中神经降压素/神经介素N mRNA反应的脱敏和增强。

Desensitization and enhancement of neurotensin/neuromedin N mRNA responses in subsets of rat caudate-putamen neurons following multiple administrations of haloperidol.

作者信息

Zahm D S, Williams E S, Krause J E

机构信息

Departments of Anatomy and Neurobiology, St. Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104, USA.

出版信息

Brain Res Mol Brain Res. 1998 Aug 31;59(2):196-204. doi: 10.1016/s0169-328x(98)00147-8.

DOI:10.1016/s0169-328x(98)00147-8
PMID:9729381
Abstract

Striatal neurons that respond to blockade of dopamine receptors with altered expression of neurotensin/neuromedin N mRNA were examined. Injections of haloperidol were given to rats at four or 24 h and both four and 24 h prior to sacrifice. Pair-matched controls were injected with equivalent volumes of vehicle at either 4 or 24 h prior to sacrifice. Sections of striatum were processed non-isotopically with a cRNA neurotensin/neuromedin N probe. Massive numbers of neurons exhibited hybridization in the lateral and dorsolateral caudate-putamen at 4 h. At 24 h, hybridized neurons were few in lateral and dorsolateral parts of the caudate-putamen, but more numerous in the dorsomedial and ventrolateral caudate-putamen than in controls. A second injection of haloperidol 4 h prior to sacrifice enhanced the dorsomedial/ventrolateral response, but failed to elicit substantial numbers of lateral and dorsolateral hybrids, as were observed at 4 h after one injection. Resistance of neurotensin expression to a second injection of haloperidol was selective for the lateral and dorsolateral parts of the caudate-putamen and may reflect residual blockade by haloperidol or altered DA receptors or second messengers. Sections subjected to immunohistochemical processing for neurotensin peptide and in situ hybridization with the neurotensin/neuromedin N mRNA probe exhibited numerous neurons in the dorsomedial and ventrolateral quadrants of the caudate-putamen that were double-labeled with immunoperoxidase and hybridization signals. This suggests that peptide synthesis, as opposed to decreased release of peptide, has a role in the accumulation of neurotensin immunoreactivity by dorsomedial and ventrolateral striatal neurons.

摘要

研究了那些对多巴胺受体阻断有反应且神经降压素/神经介素N mRNA表达改变的纹状体神经元。在处死大鼠前4小时、24小时以及4小时和24小时均给予氟哌啶醇注射。配对对照在处死前4小时或24小时注射等量的赋形剂。纹状体切片用cRNA神经降压素/神经介素N探针进行非同位素处理。4小时时,大量神经元在外侧和背外侧尾状核 - 壳核呈现杂交信号。24小时时,尾状核 - 壳核外侧和背外侧部分杂交的神经元较少,但背内侧和腹外侧尾状核 - 壳核中的杂交神经元比对照更多。处死前4小时再次注射氟哌啶醇增强了背内侧/腹外侧的反应,但未能引发如单次注射后4小时所观察到的大量外侧和背外侧杂交信号。神经降压素表达对再次注射氟哌啶醇的抗性在尾状核 - 壳核的外侧和背外侧部分具有选择性,这可能反映了氟哌啶醇的残留阻断作用或改变的多巴胺受体或第二信使。经过神经降压素肽免疫组织化学处理以及与神经降压素/神经介素N mRNA探针原位杂交的切片显示,在尾状核 - 壳核的背内侧和腹外侧象限有大量神经元同时被免疫过氧化物酶和杂交信号双标记。这表明与肽释放减少相反,肽合成在背内侧和腹外侧纹状体神经元积累神经降压素免疫反应性中起作用。

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