Bowyer J F, Frame L T, Clausing P, Nagamoto-Combs K, Osterhout C A, Sterling C R, Tank A W
Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079-9502, USA.
J Pharmacol Exp Ther. 1998 Aug;286(2):1074-85.
Four injections (intraperitoneal) of 3 mg/kg amphetamine (2 hr apart) produced pronounced hyperthermia and sustained decreases in dopamine levels and tyrosine hydroxylase (TH) protein levels in the striatum of 15-month-old male rats. A partial recovery of striatal dopamine levels was observed at 4 months after amphetamine. In contrast, TH mRNA and TH protein levels in the midbrain were unaffected at all time points tested up to 4 months after amphetamine treatment. The number of TH-immunopositive cells in the midbrain was also unchanged at 4 months after amphetamine, even though the number of TH-positive axons in the striatum remained dramatically decreased at this time point. Interestingly, TH-immunopositive cell bodies were observed 4 months after amphetamine in the lateral caudate/putamen, defined anteriorly by the genu of the corpus collosum and posteriorly by the junction of the anterior commissures; these striatal TH-positive cells were not observed in saline- or amphetamine-treated rats that did not become hyperthermic. In addition, low levels (orders of magnitude lower than that present in the midbrain) of TH mRNA were detected using reverse transcription-polymerase chain reaction in the striatum of these amphetamine-treated rats. Our results suggest that even though there is a partial recovery of striatal dopamine levels, which occurs within 4 months after amphetamine treatment, this recovery is not associated with increased TH gene expression in the midbrain. Furthermore, new TH-positive cells are generated in the striatum at this 4-month time point.
对15月龄雄性大鼠腹腔注射4次（每次间隔2小时）3毫克/千克的苯丙胺，可导致明显的体温过高，且纹状体中的多巴胺水平以及酪氨酸羟化酶（TH）蛋白水平持续下降。在注射苯丙胺4个月后，观察到纹状体多巴胺水平有部分恢复。相比之下，在苯丙胺处理后长达4个月的所有测试时间点，中脑的TH mRNA和TH蛋白水平均未受影响。即使在这个时间点纹状体中TH阳性轴突的数量仍显著减少，但在注射苯丙胺4个月后，中脑TH免疫阳性细胞的数量也没有变化。有趣的是，在注射苯丙胺4个月后，在外侧尾状核/壳核中观察到了TH免疫阳性细胞体，其前部由胼胝体膝部界定，后部由前连合的交界处界定；在未出现体温过高的生理盐水或苯丙胺处理的大鼠中未观察到这些纹状体TH阳性细胞。此外，在这些经苯丙胺处理的大鼠的纹状体中，使用逆转录聚合酶链反应检测到低水平（比中脑低几个数量级）的TH mRNA。我们的结果表明，尽管在苯丙胺处理后4个月内纹状体多巴胺水平有部分恢复，但这种恢复与中脑TH基因表达增加无关。此外，在这个4个月的时间点，纹状体中产生了新的TH阳性细胞。
