Metabolic profiling of urine and blood plasma in rat models of drug addiction on the basis of morphine, methamphetamine, and cocaine-induced conditioned place preference
Metabolic profiling of urine and blood plasma in rat models of drug addiction on the basis of morphine, methamphetamine, and cocaine-induced conditioned place preference
复制标题
DOI：
10.1007/s00216-013-7234-1
复制
发表时间：
2014-02
影响因子：
4.3
通讯作者：
K. Zaitsu;I. Miyawaki;K. Bando;H. Horie;N. Shima;M. Katagi;M. Tatsuno;T. Bamba;Takako Sato;A. Ishii;H. Tsuchihashi;Koichi Suzuki;E. Fukusaki
中科院分区：
文献类型：
--
作者：
K. Zaitsu;I. Miyawaki;K. Bando;H. Horie;N. Shima;M. Katagi;M. Tatsuno;T. Bamba;Takako Sato;A. Ishii;H. Tsuchihashi;Koichi Suzuki;E. Fukusaki
研究了吗啡(MOR)、甲基苯丙胺(MA)和可卡因(COC)诱导的条件性位置偏爱(CPP)成瘾大鼠的尿液和血浆代谢变化。用CPP模型评价每种药物的奖赏效应。应用基于MS的代谢组学方法对MOR、MA和COC成瘾大鼠的尿液和血浆进行检测。气相色谱-质谱法共鉴定出血浆中57种代谢物和尿液中70种代谢物。代谢组学方法表明，吗啡成瘾大鼠尿液中某些代谢物的含量发生了显著变化，其中包括三羧酸循环中间产物。这一结果表明能量代谢紊乱与吗啡成瘾密切相关。此外，吗啡成瘾大鼠血浆中3-羟基丁酸、L-色氨酸、半胱氨酸和正丙胺水平也有显著变化。MA成瘾大鼠的尿中乳糖、亚精胺和硬脂酸水平发生了显著变化。COC成瘾大鼠血浆中苏氨酸、胱氨酸和亚精胺水平显著升高。总而言之，代谢谱的差异暗示了MOR、MA和COC成瘾的不同生物学状态；这可能归因于药物对大脑奖励回路和由此产生的适应的不同作用。此外，研究结果还显示了通过代谢谱预测MOR成瘾程度的可能性。这是首次将代谢组学应用于药物成瘾的CPP模型的研究，我们证明了代谢组学可以成为研究药物成瘾机制的一个多方面的方法。
The metabolic profiles of urine and blood plasma in drug-addicted rat models based on morphine (MOR), methamphetamine (MA), and cocaine (COC)-induced conditioned place preference (CPP) were investigated. Rewarding effects induced by each drug were assessed by use of the CPP model. A mass spectrometry (MS)-based metabolomics approach was applied to urine and plasma of MOR, MA, and COC-addicted rats. In total, 57 metabolites in plasma and 70 metabolites in urine were identified by gas chromatography–MS. The metabolomics approach revealed that amounts of some metabolites, including tricarboxylic acid cycle intermediates, significantly changed in the urine of MOR-addicted rats. This result indicated that disruption of energy metabolism is deeply relevant to MOR addiction. In addition, 3-hydroxybutyric acid,l-tryptophan, cystine, andn-propylamine levels were significantly changed in the plasma of MOR-addicted rats. Lactose, spermidine, and stearic acid levels were significantly changed in the urine of MA-addicted rats. Threonine, cystine, and spermidine levels were significantly increased in the plasma of COC-addicted rats. In conclusion, differences in the metabolic profiles were suggestive of different biological states of MOR, MA, and COC addiction; these may be attributed to the different actions of the drugs on the brain reward circuitry and the resulting adaptation. In addition, the results showed possibility of predict the extent of MOR addiction by metabolic profiling. This is the first study to apply metabolomics to CPP models of drug addiction, and we demonstrated that metabolomics can be a multilateral approach to investigating the mechanism of drug addiction.