Castel M N, Morino P, Dagerlind A, Hökfelt T
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Eur J Neurosci. 1994 Apr 1;6(4):646-56. doi: 10.1111/j.1460-9568.1994.tb00310.x.
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.
研究了急性皮下注射甲基苯丙胺对成年大鼠纹状体中神经降压素mRNA表达的影响。在给药后的不同时间点（2、6和24小时）处死大鼠，并对来自两个纹状体水平的胶片和乳胶浸渍组织切片上的mRNA水平进行定量。甲基苯丙胺注射两小时后，在纹状体头部和尾部的不同区域均检测到神经降压素mRNA水平显著升高。在纹状体的背内侧、背外侧和腹外侧部分观察到大量阳性细胞。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。6小时后这种增加仍然存在，在纹状体头部水平与2小时处理组相似，但在尾部水平较低。甲基苯丙胺注射24小时后，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表达神经降压素mRNA的细胞显著增加，且时间进程与纹状体中观察到的相似。在第二组实验中，分别用针对神经降压素和P物质mRNA的探针评估甲基苯丙胺对相邻纹状体切片的影响。给药两小时后，观察到两种肽mRNA水平均显著增加（神经降压素增加190%，P物质增加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水平急剧、快速和短暂升高，这可能部分解释了甲基苯丙胺后在纹状体黑质通路中观察到的神经降压素肽水平升高。氟哌啶醇和甲基苯丙胺处理后观察到的表达神经降压素mRNA的细胞的不同解剖定位，以及D1受体拮抗剂SCH-23390能够抵消甲基苯丙胺对神经降压素mRNA表达的影响但不能抵消氟哌啶醇的影响这一事实，表明纹状体中至少存在两种不同的神经降压素细胞亚群。一个亚群通过D1受体调节并投射到黑质网状部。第二个亚群对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。
