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使用调味剂消退程序控制恒河猴口服乙醇摄入量并使其与行为相关

Controlled and behaviorally relevant levels of oral ethanol intake in rhesus macaques using a flavorant-fade procedure.

作者信息

Katner Simon N, Flynn Claudia T, Von Huben Stefani N, Kirsten Amber J, Davis Sophia A, Lay Christopher C, Cole Maury, Roberts Amanda J, Fox Howard S, Taffe Michael A

机构信息

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.

出版信息

Alcohol Clin Exp Res. 2004 Jun;28(6):873-83. doi: 10.1097/01.alc.0000128895.99379.8c.

Abstract

BACKGROUND

Flavorant-fading procedures can initiate and maintain oral ethanol intake in rodents. The present study developed a similar procedure to achieve controlled and behaviorally relevant levels of ethanol intake in monkeys.

METHODS

Male rhesus macaques (N = 13) were initially given the opportunity to consume 0.5 g/kg of a 1% (w/v) ethanol plus 4% (w/v) Tang solution in 1-hr limited-access sessions without the requirement of an operant response. Once consumption was stable at a particular concentration (%) and/or amount (g/kg), animals were given access to higher concentrations and/or amounts of ethanol. Animals were tested on a bimanual motor skill (BMS) task 20 and 90 min after consumption to assess behavioral impairment. Blood alcohol levels (BALs) were assessed after a session in which animals had the opportunity to consume up to 3.0 g/kg of 6% (w/v) ethanol.

RESULTS

The gradual fading up of higher concentrations and amounts of ethanol resulted in controlled and robust levels (>2.0 g/kg) of ethanol intake in half of the subjects. Increasing the concentration of the sweetener from 4 to 6% (w/v) was effective in initiating consumption in three animals. Two monkeys required the additional step of presenting the increased-sweetener solutions after a meal (postprandial consumption) to initiate significant ethanol intake. Animals were significantly impaired on the BMS task after consumption of 2.0, 2.5, and 3.0 g/kg of ethanol. Individual consumption ranging from 0.8 to 3.0 g/kg of ethanol produced BALs of 18 to 269 mg/dl.

CONCLUSIONS

The flavorant-fading procedure was effective in producing behaviorally relevant levels of ethanol consumption in rhesus macaques. This model facilitated a randomized-dose procedure to determine the behavioral effects of 0.5 to 3.0 g/kg of ethanol. This procedure therefore is of significant utility in determining behavioral or physiologic effects of specific doses of consumed ethanol in monkeys.

摘要

背景

调味剂消退程序可引发并维持啮齿动物的口服乙醇摄入量。本研究开发了一种类似程序,以在猴子中实现可控且与行为相关的乙醇摄入水平。

方法

雄性恒河猴(N = 13)最初有机会在1小时的限时进食时段内,无需操作性反应,摄入0.5克/千克的1%(重量/体积)乙醇加4%(重量/体积)的果珍溶液。一旦在特定浓度(%)和/或量(克/千克)下的摄入量稳定,动物就可接触更高浓度和/或量的乙醇。在摄入后20分钟和90分钟,对动物进行双手运动技能(BMS)任务测试,以评估行为损伤。在一次实验中,让动物有机会摄入高达3.0克/千克的6%(重量/体积)乙醇后,评估血液酒精水平(BALs)。

结果

乙醇浓度和量的逐渐增加导致一半受试者的乙醇摄入量达到可控且稳定的水平(>2.0克/千克)。将甜味剂浓度从4%(重量/体积)提高到6%(重量/体积),成功促使三只动物开始摄入乙醇。两只猴子需要额外的步骤,即在餐后提供甜味剂增加的溶液(餐后摄入),以启动显著的乙醇摄入。在摄入2.0、2.5和3.0克/千克乙醇后,动物在BMS任务中出现明显损伤。个体乙醇摄入量在0.8至3.0克/千克之间,血液酒精水平为18至269毫克/分升。

结论

调味剂消退程序有效地在恒河猴中产生了与行为相关的乙醇消费水平。该模型促进了随机剂量程序,以确定0.5至3.0克/千克乙醇的行为效应。因此,该程序在确定猴子摄入特定剂量乙醇的行为或生理效应方面具有重要实用价值。

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