Department of Surgery, Taipei City Hospital, Taipei 10431, Taiwan, Republic of China.
J Cell Biochem. 2009 Dec 15;108(6):1318-24. doi: 10.1002/jcb.22361.
Amphetamine (AMPH) is a highly addictive drug of abuse which exhibits toxicity to dopaminergic neurons in long-term abusers. Estrogen seems to show neuroprotection in dopamine (DA) deficit caused by AMPH. The present study was to investigate the effects of estradiol on the levels of striatal DA in ovariectomized (Ovx) rats treated with or without AMPH. Female rats were Ovx for 2 weeks before administration of AMPH (5 mg/kg/day, i.p.) with or without 17beta-estradiol benzoate (EB) (25 microg/kg/day, s.c.) for 7 days. The striatal tissues were collected, homogenized with DA mobile phase, and centrifuged. The concentrations of DA in the supernatants were detected by HPLC. The protein expressions of dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT-2), and tyrosine hydroxylase (TH) were analyzed by Western blotting. The results indicated that AMPH could attenuate DA level significantly in striatum (P < 0.01). Comparing to control groups, administration of either EB or EB plus AMPH increased DA level (P < 0.01). The protein expression of striatal DAT was significant greater (P < 0.01) in rats treated with AMPH plus EB than AMPH treated animals. These results suggest that the DA levels in striatum can be enhanced by EB via an increase of DAT expression following administration of AMPH.
苯丙胺（AMPH）是一种高度成瘾的滥用药物，长期滥用会对多巴胺能神经元造成毒性。雌激素似乎在 AMPH 引起的多巴胺（DA）缺乏中表现出神经保护作用。本研究旨在探讨雌二醇对 AMPH 处理的去卵巢（Ovx）大鼠纹状体 DA 水平的影响。雌性大鼠在给予 AMPH（5mg/kg/天，腹腔注射）和/或 17β-雌二醇苯甲酸酯（EB）（25μg/kg/天，皮下注射）之前进行了 2 周的 Ovx。收集纹状体组织，用 DA 流动相匀浆，离心。通过 HPLC 检测上清液中 DA 的浓度。用 Western blot 分析多巴胺转运蛋白（DAT）、囊泡单胺转运体 2（VMAT-2）和酪氨酸羟化酶（TH）的蛋白表达。结果表明，AMPH 可显著降低纹状体中的 DA 水平（P<0.01）。与对照组相比，给予 EB 或 EB 加 AMPH 均可增加 DA 水平（P<0.01）。与 AMPH 处理组相比，AMPH 加 EB 处理组大鼠纹状体 DAT 的蛋白表达显著增加（P<0.01）。这些结果表明，EB 通过增加 DAT 表达可以增强 AMPH 处理后纹状体中的 DA 水平。
