Rezvani A H, Garges P L, Miller D B, Gordon C J
Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27514.
Pharmacol Biochem Behav. 1992 Sep;43(1):103-10. doi: 10.1016/0091-3057(92)90645-v.
Alcohol preference and manifestation of alcoholism are thought by many to be associated with serotonin (5-HT) dysfunction in the brain. Thus, experiments were performed to determine the effect of acute and subchronic administration of (+/-) 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analog that stimulates 5-HT release, on alcohol preference in two strains of alcohol-preferring rats, the Fawn-Hooded (FH) and alcohol-preferring (P) rats. Rats were individually housed and provided free access to a solution of 10% ethanol, food, and water. Ethanol, food, and water intakes were measured daily. After establishing a stable baseline for ethanol and water intake, each rat was injected SC with a dose of 5.0 mg/kg MDMA or an equal volume of saline for 1 or 3 consecutive days. Body temperature was recorded immediately before and 120, 240, and 360 min after MDMA treatment. Ethanol, food, and water intake were measured for the preceding 24 h. Further, to determine the effect of MDMA on alcohol metabolism rats were injected with 5.0 mg/kg MDMA or saline and 15 min later with 2.5 g/kg alcohol. Then, blood alcohol levels were determined at 1, 3, and 5 h after alcohol administration. Our results show that a single administration of 5.0 mg/kg MDMA significantly decreased ethanol intake in both FH and P rats and increased water intake. Subchronic administration of 5.0 mg/kg MDMA for 3 consecutive days significantly attenuated alcohol intake in both strains but only increased water intake in P rats. Administration of MDMA induced hyper- and hypothermia in FH and P rats, respectively. This drug failed to exert any significant effect on the pharmacokinetics of alcohol, indicating a central effect.(ABSTRACT TRUNCATED AT 250 WORDS)
许多人认为酒精偏好和酒精中毒的表现与大脑中的血清素(5-羟色胺,5-HT)功能障碍有关。因此,进行了实验,以确定急性和亚慢性给予(±)3,4-亚甲基二氧甲基苯丙胺(摇头丸,MDMA),一种刺激5-羟色胺释放的苯丙胺类似物,对两种嗜酒大鼠品系,即黄褐 Hooded(FH)大鼠和嗜酒(P)大鼠的酒精偏好的影响。大鼠单独饲养,可自由获取10%乙醇溶液、食物和水。每天测量乙醇、食物和水的摄入量。在建立乙醇和水摄入量的稳定基线后,每只大鼠连续1天或3天皮下注射5.0mg/kg MDMA剂量或等体积的生理盐水。在MDMA治疗前以及治疗后120、240和360分钟立即记录体温。测量前24小时的乙醇、食物和水摄入量。此外,为了确定MDMA对酒精代谢的影响,给大鼠注射了5.0mg/kg MDMA或生理盐水,15分钟后注射2.5g/kg酒精。然后,在给予酒精后1、3和5小时测定血液酒精水平。我们的结果表明,单次给予5.0mg/kg MDMA显著降低了FH和P大鼠的乙醇摄入量,并增加了水的摄入量。连续3天亚慢性给予5.0mg/kg MDMA显著减弱了两个品系的酒精摄入量,但仅增加了P大鼠的水摄入量。给予MDMA分别在FH和P大鼠中引起体温过高和过低。这种药物对酒精的药代动力学没有任何显著影响,表明其作用于中枢。(摘要截断于250字)