Effects of co-administration of ketamine and ethanol on the dopamine system via the cortex-striatum circuitry.
Effects of co-administration of ketamine and ethanol on the dopamine system via the cortex-striatum circuitry.
复制标题
氯胺酮和乙醇联合给药对皮层-纹状体回路多巴胺系统的影响
DOI：
10.1016/j.lfs.2017.04.018
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发表时间：
2017
期刊：
影响因子：
6.1
通讯作者：
Zeng Xiao-Feng
中科院分区：
文献类型：
--
作者：
Liu Qing;Xu Tian-Yong;Zhang Zhi-Bi;Leung Chi-Kwan;You Ding-Yun;Wang Shang-Wen;Yi Shuai;Jing Qiang;Xie Run-Fang;Li Huifang-Jie;Zeng Xiao-Feng
氯胺酮和乙醇越来越多地被用作狂欢派对中的娱乐毒品。它们对多巴胺(DA)系统的影响在很大程度上仍不清楚。本研究旨在探讨两种不同浓度的氯胺酮加酒精和不加酒精对多巴胺系统的影响。材料与方法采用条件性位置偏爱范式，评价两种不同剂量的氯胺酮(30 mg/kg和60 mg/kg)与乙醇(0.3156 mg/kg)联合给药的奖赏效应。我们评价了联合用药对大鼠前额叶皮质(PFC)和纹状体酪氨酸羟基酶(TH)、多巴脱羧酶(DDC)、突触体相关蛋白25(SNAP25)和囊泡单胺转运体2(VMAT2)转录产物以及脑源性神经营养因子(BDNF)蛋白表达水平的影响。此外，低剂量或高剂量氯胺酮加或不加乙醇处理后，通过皮质-纹状体回路引起四个DA代谢基因的mRNA水平和细胞内BDNF蛋白丰度的不同调节反应。我们的发现可能有助于制定药物滥用患者的治疗策略。
AimKetamine and ethanol are increasingly being used together as recreational drugs in rave parties. Their effects on the dopamine (DA) system remain largely unknown. This study aimed to investigate the effects of consuming two different concentrations of ketamine with and without alcohol on the DA system.Materials and methodsWe employed the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of the combined administration of two different doses of ketamine (30 mg/kg and 60 mg/kg) with ethanol (0.3156 g/kg). We evaluated the effects of the combined drug treatment on the transcriptional output of tyrosine hydroxylase (TH), dopa decarboxylase (DDC), synaptosomal-associated protein 25 (SNAP25), and vesicular monoamine transporter 2 (VMAT2) as well as protein expression level of brain-derived neurotrophic factor (BDNF) in rat prefrontal cortex (PFC) and striatum.Key findingsWe found that rats exhibited a dose-dependent, drug-paired, place preference to ketamine and ethanol associated with an elevated DA level in the striatum but not in the PFC. Moreover, treatment involving low- or high-dose ketamine with or without ethanol caused a differential regulatory response in the mRNA levels of the four DA metabolism genes and the cellular protein abundance of BDNF via the cortex-striatum circuitry.SignificanceThis study investigated the molecular mechanisms that occur following the combined administration of ketamine and ethanol in the DA system, which could potentially lead to alterations in the mental status and behavior of ketamine/ethanol users. Our findings may aid the development of therapeutic strategies for substance abuse patients.