Martin P R, Levin S, Impeduglia G, Choe Y, Karanian J, Mukherjee A B
Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda 20892, MD.
Psychopharmacology (Berl). 1989;97(2):253-6. doi: 10.1007/BF00442259.
To determine whether prenatal thiamine deficiency, a frequent concomitant of alcoholism, reduces the response to ethanol during adulthood in the rat as does ethanol exposure in utero (Abel et al. 1981), pregnant Sprague-Dawley rats received either control or thiamine deficient diets together with daily injections of the thiamine antagonist pyrithiamine. At 7 months of age, male offspring were exposed to precisely regulated ethanol vapor concentrations in an inhalation chamber for 24 h and blood ethanol concentrations (BECs) and ethanol-induced intoxication were determined. Prenatally thiamine deficient rats and controls were indistinguishable in terms of appearance, body and liver weights, and the ratios of liver to body weight and brain to liver weight. However, total body water was significantly greater, and BECs and behavioral impairment were decreased, in the experimental rats. These findings indicate that prenatal thiamine deprivation is associated with reduced pharmacologic effect of ethanol as a result of increases in its volume of distribution and rate of metabolism.
为了确定孕期硫胺素缺乏(这是酗酒常伴随出现的情况)是否会像子宫内乙醇暴露那样(阿贝尔等人,1981年)降低大鼠成年期对乙醇的反应,怀孕的斯普拉格-道利大鼠接受了对照饮食或硫胺素缺乏饮食,并每日注射硫胺素拮抗剂吡硫胺。在7个月大时,将雄性后代置于吸入舱中,使其暴露于精确调节的乙醇蒸汽浓度下24小时,然后测定血液乙醇浓度(BECs)和乙醇诱导的中毒情况。产前硫胺素缺乏的大鼠与对照组在外观、体重和肝脏重量,以及肝脏与体重之比和大脑与肝脏重量之比方面没有差异。然而,实验大鼠的总体水含量显著更高,而BECs和行为损伤则有所降低。这些发现表明,产前硫胺素缺乏与乙醇的药理作用降低有关,这是由于其分布容积和代谢速率增加所致。