UP-REGULATION OF NEUROTENSIN MESSENGER-RNA IN THE RAT STRIATUM AFTER ACUTE METHAMPHETAMINE TREATMENT
UP-REGULATION OF NEUROTENSIN MESSENGER-RNA IN THE RAT STRIATUM AFTER ACUTE METHAMPHETAMINE TREATMENT
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DOI：
10.1111/j.1460-9568.1994.tb00310.x
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发表时间：
1994-04-01
影响因子：
3.4
通讯作者：
HOKFELT, T
中科院分区：
文献类型：
--
作者：
CASTEL, MN;MORINO, P;HOKFELT, T
在成年大鼠纹状体中研究了急性皮下注射甲基苯丙胺对神经降压素mRNA表达的影响。在给药后的不同时间点（2、6和24 h）处死大鼠，并在两个纹状体水平的胶片和乳剂浸渍组织切片上定量mRNA水平。甲基苯丙胺注射后两小时，在纹状体的不同区域，在吻侧和尾侧水平检测到神经降压素mRNA水平的急剧增加。在纹状体背内侧、背外侧和腹外侧区可见大量阳性细胞。这种上调反映了表达神经降压素mRNA的细胞数量和平均mRNA水平的增加。这种增加在6小时后仍然存在，并且在纹状体的吻侧水平与2小时处理组相似，但在尾侧水平较低。注射甲基苯丙胺后24小时，神经降压素mRNA水平恢复到对照值，或在某些区域甚至低于对照值。在嗅结节中也观察到神经降压素mRNA表达细胞的强烈增加，并且时间过程与在纹状体中观察到的时间过程相似。在第二组实验中，甲基苯丙胺的影响进行了评估，对相邻的纹状体部分与探针杂交，分别针对神经降压素和P物质的mRNA。给药后2小时，观察到两种肽mRNA水平的显著增加（神经降压素为+190%，P物质为+80%）。这些结果表明，甲基苯丙胺能够诱导纹状体神经降压素mRNA水平的急剧，快速和短暂的增加，这可能部分解释了甲基苯丙胺后在纹状体黑质途径中观察到的神经降压素肽水平的升高。氟哌啶醇和甲基苯丙胺处理后观察到的神经降压素mRNA表达细胞的不同解剖学定位，以及D1受体拮抗剂SCH-23390能够抵消甲基苯丙胺而非氟哌啶醇对神经降压素mRNA表达的影响的事实，表明纹状体中至少存在两种不同的神经降压素细胞亚群。一个群体通过D1受体调节，并投射到黑质网状部。第二个对D2受体刺激敏感，可能投射到苍白球和/或可能代表中间神经元。
The effect of acute subcutaneous administration of methamphetamine on the expression of neurotensin mRNA was investigated in the adult rat striatum. At different time points (2, 6 and 24 h) following drug administration rats were killed, and mRNA levels were quantified both on films and emulsion-dipped tissue sections from two striatal levels. Two hours after methamphetamine injection, a dramatic increase in neurotensin mRNA levels was detected in different areas of the striatum at both rostral and caudal levels. Numerous positive cells were observed in the dorsomedial, dorsolateral and ventrolateral parts of the striatum. This up-regulation reflected an increase both in the number of cells expressing neurotensin mRNA and in the mean mRNA levels. This increase was still present after 6 h and was similar to the 2 h treated group at the rostral level of the striatum, but lower at the caudal one. Twenty-four hours after methamphetamine injection, neurotensin mRNA levels were back to control values, or in some areas even below. A strong increase in neurotensin mRNA-expressing cells was also seen in the olfactory tubercle, and the time-course was similar to the one observed in the striatum. In a second set of experiments, the effect of methamphetamine was evaluated on adjacent striatal sections hybridized with probes directed against neurotensin and substance P mRNAs, respectively. Two hours after drug administration, a significant increase in the levels of both peptide mRNAs was observed (+190% for neurotensin, +80% for substance P). These results demonstrate that methamphetamine is able to induce a dramatic, rapid and transient increase in striatal neurotensin mRNA levels, which may partly account for the elevation in neurotensin peptide levels observed in the striatonigral pathway after methamphetamine. The different anatomical localization of neurotensin mRNA-expressing cells observed after haloperidol and methamphetamine treatments, as well as the fact that the D1 receptor antagonist SCH-23390 is able to counteract the effect of methamphetamine but not that of haloperidol on neurotensin mRNA expression, suggests that there are at least two different subpopulations of neurotensin cells in the striatum. One population is regulated via D1 receptors and projects to the substantia nigra pars reticulata. The second is sensitive to D2 receptor stimulation and may project to the globus pallidus and/or may represent interneurons.