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可卡因诱发的躁狂:恒河猴的明显行为和血浆浓度

Cocaine-induced rausch: overt behaviour and plasma concentrations in rhesus monkeys.

作者信息

Saady J J, Bowman E R, Aceto M D

机构信息

Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.

出版信息

Eur J Drug Metab Pharmacokinet. 1994 Jan-Mar;19(1):41-6. doi: 10.1007/BF03188822.

Abstract

This study was designed to characterize the cocaine-induced rausch or hyperarousal syndrome in rhesus monkeys. This syndrome mimics the stage observed in human abusers bingeing on cocaine and is considered crucial in the progression from recreational use to compulsive abuse. However, little research has focused on this important aspect of cocaine use. Cocaine was administered i.v. at doses of 0.0, 0.5, 1.0 and 2.0 mg/kg. Plasma concentrations were determined by gas chromatograph mass spectrometry (GC/MS) using deuterated internal standards d3 cocaine and d3 benzoylecgonine (BE). Mean plasma concentrations of cocaine, were on samples collected 1 min after infusion, 46 +/- 31, 88 +/- 15 and 275 +/- 116 mg/microliters in the 0.5, 1.0 and 2.0 mg/kg dose groups, respectively. There were no detectable concentrations of BE in any of the specimens nor was cocaine detected in the saline controls. Analysis of the behavioural data revealed that the 0.5 and 1.0 mg/kg results were intermediate between the results obtained at doses of 0.0 and 2.0 mg/kg and that the 1.0 mg/kg dose produced a higher response than the 0.5 mg/kg dose up to the 12 min. Regarding individual behavioural signs, those designated escape attempts, checking, feinting, restlessness, searching, vocalizing, chewing, crouching and wide-eyed were noted most frequently. The results showed dose-response relationships for both plasma concentrations of cocaine and for the total number of overt behavioural signs. The plasma concentrations were in the range reported for human cocaine abusers.

摘要

本研究旨在描述恒河猴中可卡因诱发的躁狂或过度兴奋综合征。该综合征模拟了人类可卡因滥用者狂欢阶段所观察到的状态,并且被认为在从消遣性使用发展到强迫性滥用的过程中至关重要。然而,很少有研究关注可卡因使用的这一重要方面。通过静脉注射给予恒河猴0.0、0.5、1.0和2.0mg/kg剂量的可卡因。使用氘代内标d3可卡因和d3苯甲酰芽子碱(BE),通过气相色谱 - 质谱联用仪(GC/MS)测定血浆浓度。在输注后1分钟采集的样本中,0.5、1.0和2.0mg/kg剂量组的可卡因平均血浆浓度分别为46±31、88±15和275±116mg/微升。在任何标本中均未检测到BE的浓度,在生理盐水对照组中也未检测到可卡因。行为数据分析表明,0.5和1.0mg/kg剂量组的结果介于0.0和2.0mg/kg剂量组所获得的结果之间,并且在长达12分钟的时间内,1.0mg/kg剂量组产生的反应高于0.5mg/kg剂量组。关于个体行为体征,那些被指定为逃跑企图、检查、佯攻、不安、搜寻、发声、咀嚼、蹲伏和睁大眼睛的体征最为常见。结果显示可卡因血浆浓度与明显行为体征总数均呈剂量反应关系。血浆浓度处于人类可卡因滥用者报道的范围内。

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