Cerebrospinal fluid neurotransmitter levels and central nervous system depression in a rat drug overdose model

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2020-02-01 DOI:10.1080/15376516.2019.1672122

Hiroshi Tsutsumi, K. Yonemitsu, Ako Sasao, Y. Ohtsu, Shota Furukawa, Y. Nishitani

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引用次数: 3

Abstract

Abstract A neuropsychiatric drug overdose impairs physiological function via central nervous system (CNS) depression. In drug-related deaths, only the drug concentration can currently provide information regarding CNS depression in victims. In this study, using a drug overdose model, we investigated the ability of neurotransmitters in the cerebrospinal fluid (CSF) to serve as biomarkers for CNS depression. Four groups of rats were orally administered diazepam (200 mg/kg) and/or phenobarbital (100 mg/kg) or vehicle. In a hot plate test performed to assess physiological impairment, drug-administered animals showed prolongation of the response latency. Serum drug concentrations were also sufficient to observe the effect of drug overdose. The levels of benzoyl-derivatized neurotransmitters were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis. Noradrenaline, adrenaline, serotonin, melatonin, phosphoethanolamine, and histamine levels in the CSF decreased as the response latencies in the hot plate test increased. These reduced CSF neurotransmitter levels may represent physiological dysfunction through CNS depression.

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大鼠药物过量模型的脑脊液神经递质水平和中枢神经系统抑制

神经精神药物过量可通过中枢神经系统(CNS)抑郁损害生理功能。在药物相关死亡中，目前只有药物浓度可以提供有关受害者中枢神经系统抑郁的信息。在这项研究中，使用药物过量模型，我们研究了脑脊液(CSF)中神经递质作为中枢神经系统抑郁生物标志物的能力。四组大鼠分别口服安定(200 mg/kg)和/或苯巴比妥(100 mg/kg)或对照药。在评估生理损伤的热板试验中，给药的动物表现出反应潜伏期的延长。血清药物浓度也足以观察药物过量的影响。采用液相色谱-串联质谱(LC-MS/MS)分析方法测定苯甲酰衍生神经递质水平。去甲肾上腺素、肾上腺素、血清素、褪黑素、磷酸乙醇胺和组胺水平随着热板试验反应潜伏期的增加而降低。脑脊液神经递质水平降低可能通过中枢神经系统抑制而表现出生理功能障碍。

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来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.