Protective effects of cholecystokinin-8 on methamphetamine-induced behavioral changes and dopaminergic neurodegeneration in mice
Protective effects of cholecystokinin-8 on methamphetamine-induced behavioral changes and dopaminergic neurodegeneration in mice
复制标题
胆囊收缩素-8 对甲基苯丙胺诱导的小鼠行为改变和多巴胺能神经变性的保护作用
DOI：
10.1016/j.bbr.2015.01.028
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发表时间：
2015-04-15
影响因子：
2.7
通讯作者：
Cong, Bin
中科院分区：
文献类型：
--
作者：
Gou, Hongyan;Wen, Di;Cong, Bin
我们研究了神经肽胆囊收缩素-8预处理是否影响甲基苯丙胺（METH）诱导的雄性C57/BL6小鼠的行为改变和多巴胺能神经变性。单独的CCK-8预处理对运动和刻板行为没有影响，也不能诱导行为致敏；然而，它以剂量依赖的方式减弱了低剂量甲基苯丙胺（1mg /kg）诱导的过度运动和行为致敏。CCK-8在剂量为3 mg/kg而不是10 mg/kg时减弱甲基甲醚诱导的刻板行为。CCK-8预处理能减弱甲基安非他明（10 mg/kg）诱导的高温，减少纹状体中酪氨酸羟化酶（TH）和多巴胺转运蛋白（DAT），以及黑质中TH的表达。单独CCK-8对直肠温度、黑质纹状体区TH和DAT表达无影响。综上所述，我们的研究表明，CCK-8预处理可以抑制由甲基安非他明反复暴露引起的典型变化，如过度运动、行为致敏、刻板行为和多巴胺能神经毒性。这些发现使CCK-8成为治疗与甲基苯丙胺滥用相关的多种症状的潜在治疗剂。(C) 2015 Elsevier B.V.版权所有
We investigated whether pretreatment with the neuropeptide cholecystokinin-8 affected methamphetamine (METH)-induced behavioral changes and dopaminergic neurodegeneration in male C57/BL6 mice. CCK-8 pretreatment alone had no effect on locomotion and stereotypic behavior and could not induce behavioral sensitization; however, it attenuated, in a dose-dependent manner, hyperlocomotion and behavioral sensitization induced by a low dose of METH (1 mg/kg). CCK-8 attenuated METH-induced stereotypic behavior at a dose of 3 mg/kg but not at 10 mg/kg. CCK-8 pretreatment attenuated METH (10 mg/kg)-induced hyperthermia, the decrease of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum, and TH in the substantia nigra. CCK-8 alone had no effect on rectal temperature, TH and DAT expression in the nigrostriatal region. In conclusion, our study demonstrated that pretreatment with CCK-8 inhibited changes typically induced by repeated exposure to METH, such as hyperlocomotion, behavioral sensitization, stereotypic behavior, and dopaminergic neurotoxicity. These findings make CCK-8 a potential therapeutic agent for the treatment of multiple symptoms associated with METH abuse. (C) 2015 Elsevier B.V. All rights reserved.