Cappon G D, Broening H W, Pu C, Morford L, Vorhees C V
Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH 45229-3039, USA.
Synapse. 1996 Oct;24(2):173-81. doi: 10.1002/(SICI)1098-2396(199610)24:2<173::AID-SYN9>3.0.CO;2-C.
Methamphetamine (MA) administration to adult rats (4 x 10 mg/kg s.c.) induces neurotoxicity predominately characterized by a persistent reduction of neostriatal dopamine (DA) content. Hyperthermia following MA administration potentiates the resulting DA depletion. DA-derived free radicals are postulated to be a mechanism through which MA-induced neurotoxicity is produced. The spin trapping agent PBN reacts with free radicals to form nitroxyl adducts, thereby preventing damaging free radical reactions with cellular substrates. MA with saline pretreatment (Sal-MA) reduced neostriatal DA by 55% (P < 0.01 vs. Sal-Sal). MA with PBN pretreatment (PBN-MA) at 36 or 60 mg/kg reduced neostriatal DA by 36 and 22%, respectively (P < 0.05 and P < 0.01 vs Sal-MA) indicating partial protection. PBN pretreatment did not alter MA-induced hyperthermia. Thus, PBN does not attenuate MA-induced neurotoxicity by reducing MA-induced hyperthermia. These results support a role for free radicals in the generation of MA-induced dopaminergic neurotoxicity.
给成年大鼠皮下注射甲基苯丙胺（MA，4×10毫克/千克）会诱发神经毒性，其主要特征是新纹状体多巴胺（DA）含量持续减少。MA给药后出现的体温过高会增强由此导致的DA耗竭。据推测，DA衍生的自由基是MA诱发神经毒性产生的一种机制。自旋捕获剂PBN与自由基反应形成硝酰加合物，从而防止自由基与细胞底物发生破坏性反应。用生理盐水预处理的MA（Sal-MA）使新纹状体DA减少了55%（与Sal-Sal相比，P<0.01）。用36或60毫克/千克的PBN预处理的MA（PBN-MA）分别使新纹状体DA减少了36%和22%（与Sal-MA相比，P<0.05和P<0.01），表明有部分保护作用。PBN预处理并未改变MA诱发的体温过高。因此，PBN不会通过降低MA诱发的体温过高来减轻MA诱发的神经毒性。这些结果支持自由基在MA诱发的多巴胺能神经毒性产生过程中起作用。
