Grant Kathleen A, Leng Xiaoyan, Green Heather L, Szeliga Kendall T, Rogers Laura S M, Gonzales Steven W
Integrative Neuroscience Initiative on Alcoholism, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Alcohol Clin Exp Res. 2008 Oct;32(10):1824-38. doi: 10.1111/j.1530-0277.2008.00765.x. Epub 2008 Aug 12.
We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption.
Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months.
Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent "spree" drinking (intakes >4.0 g/kg/d).
This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the equivalent of 6 drinks) that evolve into chronic heavy alcohol consumption in primates (drinking the equivalent of 16 to 20 drinks per day). The model may aid in identifying biological risks for establishing harmful alcohol drinking.
我们开发了一种酒精自我给药动物模型,该模型最初采用定时诱导多饮(SIP)来在开放获取(每天22小时)条件下建立可靠的乙醇消耗,同时提供食物和水。SIP是一种辅助行为,由限制获取重要商品(如调味食品)产生。在这些条件下产生的诱导方案和乙醇多饮为研究导致慢性过量饮酒的饮酒类型发展提供了机会。
成年雄性食蟹猴通过固定时间300秒(FT-300秒)的香蕉味颗粒给药方案诱导饮水和饮用4%(w/v,溶于水)乙醇。FT-300秒方案连续实施120次,每日诱导剂量每30天从0.0克/千克增加到0.5克/千克,再到1.0克/千克,最后到1.5克/千克。诱导后,猴子被允许每天22小时同时获取4%(w/v)乙醇和水,持续12个月。
在诱导饮用1.5克/千克乙醇期间出现的饮酒类型能够高度预测接下来12个月的每日乙醇摄入量。具体而言,猴子在诱导期间摄入1.5克/千克乙醇且饮酒间隔不超过5分钟(定义为一次饮酒发作)的频率与接下来12个月开放获取乙醇期间的后续乙醇摄入量密切相关(相关性为0.91)。诱导期间的血液乙醇含量与摄入量和饮酒类型高度相关,当猴子一次饮用1.5克/千克剂量时,血液乙醇含量范围为100至160毫克%。40%的猴子成为重度饮酒者(12个月内平均每日摄入量>3.0克/千克),其特征为频繁“狂饮”(摄入量>4.0克/千克/天)。
这种乙醇自我给药模型识别出早期饮酒类型(一口气喝下相当于6杯酒的量),这些类型会发展为灵长类动物的慢性重度饮酒(每天饮用相当于16至20杯酒的量)。该模型可能有助于识别形成有害饮酒习惯的生物学风险。