Weed Michael R, Wilcox Kristin M, Ator Nancy A, Hienz Robert D
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218, USA.
Alcohol Clin Exp Res. 2008 Jun;32(6):942-51. doi: 10.1111/j.1530-0277.2008.00652.x. Epub 2008 Apr 26.
Alcohol abuse is a major public health burden that can lead to many adverse health effects such as impaired hepatic, gastrointestinal, central nervous system and immune system function. Preclinical animal models of alcohol abuse allow for experimental control over variables often difficult to control in human clinical studies (e.g., ethanol exposure before or during the study, history of other drug use, access to medical care, nutritional status, etc). Nonhuman primate models in particular provide increased genetic, anatomic and physiologic similarity to humans, relative to rodent models. A small percentage of macaques will spontaneously consume large quantities of ethanol; however, most nonhuman primate models of "voluntary" ethanol intake produce relatively low daily ethanol intake in the majority of monkeys.
To facilitate study of chronic exposure to high levels of ethanol intake, a macaque model has been developed that induces consistent, daily high-level ethanol consumption. This multiple-session procedure employed 4 drinking sessions per day, with sessions occurring once every 6 hours.
The group average alcohol consumption was 4.6 g/kg/d (SEM 0.4), roughly twice the group average consumption of previous reports. Ethanol drinking sessions produced group mean blood ethanol levels of 95 mg/dl after 60 minutes, and fine motor control was impaired up to 90 minutes after a drinking session.
This model of multiple-session, limited access, oral ethanol self-dosing produced consistent, high-level ethanol consumption with each session qualifying as a "binge" drinking session using the definition of "binge" provided by the NIAAA (>80 mg/dl/session). This model of ethanol drinking in macaques will be of great utility in the study of immunological, physiological and behavioral effects of ethanol in nonhuman primates.
酒精滥用是一项重大的公共卫生负担,可导致许多不良健康影响,如肝脏、胃肠道、中枢神经系统和免疫系统功能受损。酒精滥用的临床前动物模型允许对人类临床研究中通常难以控制的变量进行实验控制(例如,研究前或研究期间的乙醇暴露、其他药物使用史、获得医疗护理的机会、营养状况等)。特别是与啮齿动物模型相比,非人灵长类动物模型在基因、解剖学和生理学上与人类的相似性更高。一小部分猕猴会自发大量摄入乙醇;然而,大多数“自愿”摄入乙醇的非人灵长类动物模型在大多数猴子中产生的每日乙醇摄入量相对较低。
为便于研究长期暴露于高水平乙醇摄入,已开发出一种猕猴模型,该模型可诱导持续的每日高水平乙醇消费。这个多阶段程序每天进行4次饮酒阶段,每6小时进行一次。
该组平均酒精消费量为4.6克/千克/天(标准误0.4),大约是先前报告中该组平均消费量的两倍。乙醇饮用阶段在60分钟后使组平均血液乙醇水平达到95毫克/分升,并且在饮用阶段后长达90分钟精细运动控制受到损害。
这种多阶段、有限接触、口服乙醇自我给药的模型产生了持续的高水平乙醇消费,根据美国国立酒精滥用与酒精中毒研究所提供的“暴饮”定义(>80毫克/分升/阶段),每个阶段都可被视为一次“暴饮”饮酒阶段。这种猕猴乙醇饮用模型在研究乙醇对非人灵长类动物的免疫、生理和行为影响方面将具有很大的实用性。