Tsai Y F, Tsai H W, Tai M Y
Department of Physiology, College of Medicine, National Taiwan University, Taipei, ROC.
Neurosci Res. 1994 Jul;20(1):27-33. doi: 10.1016/0168-0102(94)90019-1.
Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopamine levels in the striatum (ST), substantia nigra (SN), olfactory tubercle (OT), ventral tegmental area (VTA) and nucleus accumbens (NA) were studied in young (1 month) and old (21 months) male Long-Evans rats. Following repeated treatment with MPTP at low dose (3 mg/kg i.p. daily for 8 days) both young and old rats showed a marked depletion of dopamine (DA) concentrations in the ST compared to those of age-matched saline-treated controls. However, a significant reduction in DA levels was observed in the OT and NA of old but not young rats treated with MPTP. In contrast, no changes in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in these three regions were seen in either young or old MPTP-treated rats. However, the ratio of DOPAC/DA and HVA/DA in the ST and NA were significantly higher in old MPTP-treated rats than those in old controls. The concentrations of DA, DOPAC and HVA remained unchanged in the SN and VTA of both young and old rats after MPTP treatment. These results indicate that multiple treatment of low-dose MPTP selectively causes more widespread damage to dopaminergic neurons in old rats than in young ones, and further support the view that effects of MPTP on the dopaminergic system in rats may depend on age.
研究了1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）对年轻（1个月）和老年（21个月）雄性Long-Evans大鼠纹状体（ST）、黑质（SN）、嗅结节（OT）、腹侧被盖区（VTA）和伏隔核（NA）中多巴胺水平的影响。在低剂量MPTP重复处理（3mg/kg腹腔注射，每日1次，共8天）后，与年龄匹配的生理盐水处理对照组相比，年轻和老年大鼠的ST中多巴胺（DA）浓度均显著降低。然而，MPTP处理的老年大鼠而非年轻大鼠的OT和NA中DA水平显著降低。相比之下，MPTP处理的年轻和老年大鼠在这三个区域的3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）水平均无变化。然而，MPTP处理的老年大鼠ST和NA中DOPAC/DA和HVA/DA的比值显著高于老年对照组。MPTP处理后，年轻和老年大鼠的SN和VTA中DA、DOPAC和HVA的浓度均保持不变。这些结果表明，低剂量MPTP的多次处理对老年大鼠多巴胺能神经元的选择性损伤比年轻大鼠更广泛，并进一步支持MPTP对大鼠多巴胺能系统的影响可能取决于年龄的观点。
