Eisch A J, Marshall J F
Department of Psychobiology, University of California, Irvine 92697-4550, USA.
Synapse. 1998 Dec;30(4):433-45. doi: 10.1002/(SICI)1098-2396(199812)30:4<433::AID-SYN10>3.0.CO;2-O.
Methamphetamine (m-AMPH) administration injures both striatal dopaminergic terminals and certain nonmonoaminergic cortical neurons. Fluoro-Jade histochemistry was used to label cortical cells injured by m-AMPH in order to identify factors that contribute to the cortical cell body damage. Rats given four injections of m-AMPH (4 mg/kg) at 2-h intervals showed hyperthermia (mean = 40.0 +/- 0.10 degrees C) and increased behavioral activation relative to animals given saline (SAL). Three days later, m-AMPH-treated animals showed indices of injury to striatal DA terminals (depletion of tyrosine hydroxylase immunoreactivity) and parietal cortical cell bodies (appearance of Fluoro-Jade stained cells). Pretreatment with a dopamine (DA) D1, D2, or N-methyl-D-aspartate (NMDA) receptor antagonist, or administration of m-AMPH in a 4 degrees C environment, prevented or attenuated m-AMPH-induced hyperthermia, behavioral activation, and injury to striatal DA terminals and parietal cortical cell bodies. Animals pretreated with a DA transport inhibitor prior to m-AMPH showed hyperthermia, behavioral activation, and parietal cortical cell body injury, but they did not show striatal DA terminal injury. Pretreatment with a 5HT transport inhibitor failed to prevent m-AMPH-induced damage to striatal DA terminals or parietal cortical cell bodies. Animals given four injections of SAL in a 37 degrees C environment became hyperthermic, but showed no injury to striatal DA terminals or cortical cell bodies. The ability of the DA transport inhibitor to block m-AMPH-induced striatal DA damage, but not cortical injury, and the inability of hyperthermia alone to cause the cortical cell body injury suggests that m-AMPH-induced behavioral activation and hyperthermia may both be necessary for the subsequent parietal cortical cell body damage.
给予甲基苯丙胺（m-AMPH）会损伤纹状体多巴胺能终末和某些非单胺能皮质神经元。使用荧光玉组织化学法标记受m-AMPH损伤的皮质细胞，以确定导致皮质细胞体损伤的因素。以2小时间隔给予四次m-AMPH（4毫克/千克）的大鼠相对于给予生理盐水（SAL）的动物出现体温过高（平均=40.0±0.10摄氏度）和行为激活增加。三天后，接受m-AMPH治疗的动物出现纹状体多巴胺能终末损伤指标（酪氨酸羟化酶免疫反应性耗竭）和顶叶皮质细胞体损伤指标（荧光玉染色细胞出现）。用多巴胺（DA）D1、D2或N-甲基-D-天冬氨酸（NMDA）受体拮抗剂预处理，或在4摄氏度环境中给予m-AMPH，可预防或减轻m-AMPH诱导的体温过高、行为激活以及对纹状体多巴胺能终末和顶叶皮质细胞体的损伤。在给予m-AMPH之前用DA转运抑制剂预处理的动物出现体温过高、行为激活和顶叶皮质细胞体损伤，但未出现纹状体多巴胺能终末损伤。用5-羟色胺转运抑制剂预处理未能预防m-AMPH对纹状体多巴胺能终末或顶叶皮质细胞体的损伤。在37摄氏度环境中给予四次SAL的动物体温过高，但未出现纹状体多巴胺能终末或皮质细胞体损伤。DA转运抑制剂能够阻断m-AMPH诱导的纹状体多巴胺损伤，但不能阻断皮质损伤，且单纯体温过高无法导致皮质细胞体损伤，这表明m-AMPH诱导的行为激活和体温过高可能都是随后顶叶皮质细胞体损伤所必需的。
