Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, 19 Xinjiekouwai Street, Haidian district, Beijing, China.
Chinese PLA General Hospital, Beijing, China.
BMC Complement Altern Med. 2018 Feb 23;18(1):76. doi: 10.1186/s12906-018-2094-z.
Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function.
Immunohistochemical staining and/or autoradiography staining were used to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and TH levels in the striatum. Using a stereotyped behavior rating scale, we evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization.
Repeated METH administration induced obvious stereotyped behavior and neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly attenuated METH-induced stereotyped responses, and interdicted METH-induced changes in the levels of DAT, D2R and TH expression. Treatment with JTT after METH administration restored DAT, D2R and TH expression to normal levels.
Our results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.
甲基苯丙胺（METH）是一种具有高滥用倾向的精神兴奋剂，会影响单胺神经递质系统，尤其是多巴胺系统。目前，尚无有效的药物可用于治疗 METH 滥用，以恢复 METH 引起的多巴胺能功能障碍。Jitai 片（JTT）是一种商业性的中药制剂，已被证明可调节海洛因成瘾者和吗啡依赖大鼠的多巴胺能功能。本研究的目的是在啮齿动物模型中研究 JTT 是否能预防 METH 诱导的神经毒性，以及/或恢复 METH 损伤的多巴胺能功能。
免疫组织化学染色和/或放射自显影染色用于检测黑质中的酪氨酸羟化酶（TH）表达，并检测纹状体中的多巴胺转运蛋白（DAT）、多巴胺 D2 受体（D2R）和 TH 水平。使用刻板行为评分量表评估 JTT 对 METH 诱导的行为敏化的抑制作用。
重复 METH 给药会引起明显的刻板行为和多巴胺能系统的神经毒性。JTT 预处理显著减弱了 METH 诱导的刻板反应，并阻止了 METH 诱导的 DAT、D2R 和 TH 表达水平的变化。在 METH 给药后给予 JTT 治疗可使 DAT、D2R 和 TH 表达恢复正常水平。
我们的结果表明，JTT 可预防 METH 诱导的神经毒性并恢复多巴胺能功能，因此可能是治疗与 METH 滥用相关的多巴胺能缺陷的潜在治疗方法。
