Kita T, Paku S, Takahashi M, Kubo K, Wagner G C, Nakashima T
Department of Pharmacology, Nara Medical University, Kashihara, Japan.
Neuropharmacology. 1998 Sep;37(9):1177-84. doi: 10.1016/s0028-3908(98)00106-3.
Repeated administration of methamphetamine (METH; 2 and 4 mg/kg, s.c. four times every 2 h) caused hyperthermia and a dose-dependent depletion of striatal dopamine levels 3 days after the METH-treatment in both BALB/cAnNCrj (BALB) and DBA/2NCrj (DBA) mice, but these responses were lower in C57BL/6NCrj (C57BL) mice. An acute decrease of striatal dopamine levels 30 min after the last injection of METH (4 mg/kg) was observed in both BALB and DBA mice, while an increase in dopamine was observed in C57BL mice. Striatal 3-methoxytyramine levels were drastically increased in both DBA and C57BL mice after this same treatment. Moreover, pretreatment with the superoxide dismutase inhibitor, diethyldithiocarbamate (200 mg/kg, i.p.) exacerbated the METH (4 mg/kg)-induced striatal dopamine-depletion in BALB mice. In addition, pretreatment with an inhibitor of poly(ADP-ribose) polymerase, benzamide (160 mg/kg, s.c.), significantly attenuated the METH (4 mg/kg)-induced striatal dopamine depletion in both BALB and DBA mice. These results suggest that both BALB and DBA mice possess a higher sensitivity to the METH-induced striatal dopaminergic neurotoxicity compared to C57BL mice. In addition, the striatal dopaminergic neurons of BALB mice may be more vulnerable to METH-induced oxidative stress as compared to that in C57BL mice.
对BALB/cAnNCrj（BALB）和DBA/2NCrj（DBA）小鼠皮下注射甲基苯丙胺（METH；2和4mg/kg，每2小时4次），连续给药后，在METH处理3天后会引起体温过高和纹状体多巴胺水平呈剂量依赖性降低，但这些反应在C57BL/6NCrj（C57BL）小鼠中较低。在BALB和DBA小鼠中，末次注射METH（4mg/kg）30分钟后，纹状体多巴胺水平急性降低，而在C57BL小鼠中观察到多巴胺增加。相同处理后，DBA和C57BL小鼠纹状体3-甲氧基酪胺水平均大幅升高。此外，用超氧化物歧化酶抑制剂二乙基二硫代氨基甲酸盐（200mg/kg，腹腔注射）预处理会加剧METH（4mg/kg）诱导的BALB小鼠纹状体多巴胺耗竭。另外，用聚（ADP-核糖）聚合酶抑制剂苯甲酰胺（160mg/kg，皮下注射）预处理可显著减轻METH（4mg/kg）诱导的BALB和DBA小鼠纹状体多巴胺耗竭。这些结果表明，与C57BL小鼠相比，BALB和DBA小鼠对METH诱导的纹状体多巴胺能神经毒性具有更高的敏感性。此外，与C57BL小鼠相比，BALB小鼠的纹状体多巴胺能神经元可能对METH诱导的氧化应激更敏感。
