O'Dell Steven J, Marshall John F
Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
Synapse. 2002 Feb;43(2):122-30. doi: 10.1002/syn.10016.
Repeated methamphetamine (mAMPH) damages forebrain monoamine terminals and causes degeneration of nonmonoaminergic cell bodies in rat primary somatosensory cortex (S1). These degenerating cortical neurons can be labeled with the fluorochrome dye Fluoro-Jade (FJ) and are found almost exclusively in layers II/III and IV of the vibrissae representation in S1. Within S1, layer IV is organized into discrete, anatomically identifiable units termed barrels, each of which receives information from a single whisker. We previously reported that mAMPH-damaged neurons in S1 were located within the whisker barrels, suggesting that the prolonged mAMPH-induced whisking contributes to S1 neuronal injury. Here, we investigate effects of vibrissae removal on mAMPH-induced damage to S1 neurons. Rats were anesthetized and vibrissae were trimmed from either the left, right, or neither side of the snout. The next day they were given four injections of either saline (1 ml/kg, s.c.) or mAMPH (4 mg/kg, s.c.) at 2-h intervals. Three days later, cortical sections were processed for FJ histochemistry. The hemivibrissotomy produces a hemispheric asymmetry in FJ-positive neurons in barrel cortex, with fewer damaged neurons contralateral than ipsilateral to whisker removal. Taken together with the demonstration that acute injection of this dose of mAMPH induces the immediate early gene zif/268 and Fos protein in barrel cortex, these data suggest that the prolonged behavioral activity involving the vibrissae contributes to the mAMPH-induced damage to S1 neurons. Thus, some of the injurious effects of drugs may depend on afferent activity occurring as a result of the abnormal behaviors evoked by their administration.
反复给予甲基苯丙胺（mAMPH）会损害大鼠初级体感皮层（S1）的前脑单胺能终末，并导致非单胺能细胞体变性。这些变性的皮层神经元可用荧光染料氟玉髓（FJ）标记，且几乎只在S1中触须表征的第II/III层和第IV层中发现。在S1内，第IV层被组织成离散的、解剖学上可识别的单元，称为桶状结构，每个桶状结构接收来自单个触须的信息。我们之前报道过，S1中受mAMPH损伤的神经元位于触须桶状结构内，这表明mAMPH诱导的长时间触须运动有助于S1神经元损伤。在此，我们研究去除触须对mAMPH诱导的S1神经元损伤的影响。将大鼠麻醉，从口鼻的左侧、右侧或两侧都不修剪触须。第二天，它们每隔2小时接受四次注射，分别是生理盐水（1毫升/千克，皮下注射）或mAMPH（4毫克/千克，皮下注射）。三天后，对皮层切片进行FJ组织化学处理。半侧触须切断术在桶状皮层中FJ阳性神经元产生半球不对称性，与去除触须同侧相比，对侧受损神经元较少。结合急性注射该剂量mAMPH可在桶状皮层诱导即刻早期基因zif/268和Fos蛋白的证明，这些数据表明涉及触须的长时间行为活动有助于mAMPH诱导的S1神经元损伤。因此，药物的一些有害作用可能取决于其给药引发的异常行为所导致的传入活动。
