Myers R D, Critcher E C
Pharmacol Biochem Behav. 1982 May;16(5):827-36. doi: 10.1016/0091-3057(82)90243-x.
In male rats of the Sprague-Dawley or Long-Evans strain, intracerebroventricular (ICV) cannulae were implanted permanently using stereotaxic techniques. Tetrahydropapaveroline (THP) was infused ICV for up to 14 days either chronically around the clock or acutely once per day in doses previously found to induce an abnormally high intake of alcohol. During these periods, alcohol preference for individual rats was determined by a self-selection procedure in which the concentration of alcohol was increased from 3 to 30% on each day of a 12-day interval. Those rats which displayed a substantial increase in their intake of alcohol were selected for naloxone treatment and subsequently assigned a fixed concentration of alcohol at which maximum consumption occurred. Naloxone was administered subcutaneously two to six times per day for three consecutive days in total daily doses ranging from 1.5 to 3.0 mg/kg. Each rat served as its own control and was given 0.9% saline isovolumetrically according to the same temporal schedule. Naloxone generally suppressed alcohol intake in animals by 20% to 45%, but the reduction in drinking depended upon the injection regimen as well as the prior level of alcohol consumption. In "high drinking" rats, the mean alcohol intake of 6.2 g/kg/day was reduced to 3.7 g/kg/day by naloxone whereas in "low drinkers" the mean intake of 3.5 g/kg/day was suppressed to 2.8 g/kg/day by the opiate antagonist. These results further support the suggestion of a possible opiate receptor link in the pathogenesis and maintenance of aberrant drinking of alcohol, the mechanism of which may involve the endogenous action of an amine-aldehyde condensation product in the brain.
在斯普拉格-道利或长-伊文斯品系的雄性大鼠中，采用立体定位技术永久性植入脑室内（ICV）套管。将四氢罂粟碱（THP）以先前发现可诱导酒精摄入量异常高的剂量，连续14天进行慢性全天候或每天急性一次注入脑室内。在此期间，通过自我选择程序确定个体大鼠对酒精的偏好，在12天的间隔期内，每天将酒精浓度从3%提高到30%。选择那些酒精摄入量大幅增加的大鼠进行纳洛酮治疗，随后给予其出现最大消耗量时的固定酒精浓度。纳洛酮每天皮下注射2至6次，连续3天，总日剂量为1.5至3.0mg/kg。每只大鼠作为自身对照，按照相同的时间安排等量给予0.9%生理盐水。纳洛酮通常可使动物的酒精摄入量降低20%至45%，但饮酒量的减少取决于注射方案以及先前的酒精消耗水平。在“高饮酒量”大鼠中，纳洛酮将平均酒精摄入量从6.2g/kg/天降至3.7g/kg/天，而在“低饮酒量”大鼠中，阿片类拮抗剂将平均摄入量从3.5g/kg/天抑制至2.8g/kg/天。这些结果进一步支持了在酒精异常饮酒的发病机制和维持过程中可能存在阿片受体联系的观点，其机制可能涉及大脑中胺醛缩合产物的内源性作用。
