胎儿酒精谱系障碍

胎儿酒精谱系障碍是指由于孕期酒精暴露而产生的一系列影响的总称,涵盖了胎儿酒精中毒综合症、酒精相关神经系统发育障碍和酒精相关出生缺陷等.它是目前已知的导致智力发育迟缓的主要原因.患者在成长过程中可能遇到一系列的问题.对胎儿酒精谱系障碍的诊断非常困难,目前只有胎儿酒精中毒综合症有明确的诊断指标.胎儿酒精谱系障碍的唯一病因是怀孕期间的酒精摄入.在国内外,孕妇在孕期频繁饮酒及酗酒的情况仍不断发生.通过有效手段的干预,胎儿酒精谱系障碍是可以100%预防的.     

胆碱对酒精中毒孕鼠神经元保护作用的实验研究

目的:观察不同剂量胆碱对孕期酒精中毒大鼠生仔后神经元的影响,探讨其机制。方法:将孕鼠分为酒精组、大剂量胆碱组、小剂量胆碱组及对照组。用灌胃法建立酒精中毒动物模型。在分娩当天进行行为测试,分别观察母鼠的舔仔行为和哺乳行为,计算各行为时间,比较各组母鼠的行为的差异。用免疫组化方法检测下丘脑室旁核催产素神经元数量变化。结果:酒精组母鼠的行为持续时间与对照组比较差异有显著性(P<0.01或P<0.05);胆碱组的行为持续时间与酒精组比较差异有显著性(P<0.01或P<0.05);与对照组比较,酒精组和小剂量胆碱保护组PVN区催产素神经元阳性细胞数目减少(P<0.05)。结论:怀孕期大量饮酒能够明显损伤相关的催产素神经元,而胆碱对神经元有一定的保护作用,并具有一定的剂量依从性,其机制可能是足量的胆碱为脑细胞提供了一定的营养,有效的保持了细胞结构。     

新生大鼠脑室周围白质软化模型的建立及评价

目的建立2d龄SD大鼠脑室周围白质软化(periventricular leukomalacia,PVL)模型,并进行评价。方法将2d龄SD大鼠84只随机分为对照组和PVL模型组。对照组仅进行右侧颈总动脉分离术,而不作结扎及缺氧处理。PVL模型组大鼠行右侧颈总动脉结扎后,吸入含6%O2和94%N2的氧氮混合气体处理4h,建立新生大鼠PVL模型。对两组进行形态学观察及神经行为学评价和生长发育评估。结果光镜和电镜下发现,对照组无明显形态学变化而缺氧缺血48h后PVL组有显著的脑室周围脑白质损伤,14d可见典型的PVL病理改变。神经行为学评价,PVL组大鼠感觉运动功能、情感行为能力及生长发育均较对照组明显减退。结论该模型的建立是成功的,符合早产儿PVL改变。     

酒精和洗衣粉对皮肤屏障功能的影响

研究了酒精和洗衣粉对皮肤屏障功能的影响。发现70%酒精浸泡新生大鼠离体皮肤10分钟或70%酒精喷洒新生大鼠皮肤保留10分钟,均引起皮肤屏障功能改变。0.01～1%浓度洗衣粉水溶液浸泡新生大鼠离体皮肤10分钟或新生大鼠离体皮肤接触0.01～1%浓度洗衣粉溶液4小时,未发现皮肤屏障功能有异常。结果提示,日常生活中使用洗衣粉(0.1～0.3%浓度)是安全的,使用70%酒精作皮肤消毒剂,要加强保护皮肤,免受有害物质侵蚀。     

孕期铅暴露对子代大鼠情感行为及学习记忆变化的实验研究

[目的]观察孕期铅暴露对子代大鼠脑海马区神经元、细胞器超微结构及神经突触形态学参数变化,探讨孕期铅暴露对子代大鼠学习记忆损害的可能机制. [方法] 通过孕鼠自由饮用0.1％及0.2％醋酸铅溶液的方法建立模型,其雄性子代分别为低剂量铅暴露组(LG)及高剂量铅暴露组(HG),同时设立正常对照组(NG),每组9～12只大鼠.子代大鼠出生后36日龄应用透射电镜分别观察海马CA1区神经元、细胞器的病理超微结构改变和神经突触参数变化特征. [结果]铅暴露仔鼠脑海马区出现显著病理超微结构改变.HG组在神经元变性坏死、线粒体肿胀、内质网脱颗粒及高尔基体扩张等方面较对照组程度严重,差异有高度统计学意义(P＜0.05或＜0.01).三组在突触后致密物质厚度、突触活性带长度、突触界面曲率及突触间隙等方面的差异有高度统计学意义(P均＜0.01),提示铅暴露仔鼠脑海马CA1区突触后致密物质厚度减小、突触活性带长度缩短、突触界面曲率下降及突触间隙增宽.铅暴露组与对照组在突触数密度及面密度方面差异无统计学意义(P均＞0.05). [结论]孕期铅暴露可导致子代大鼠脑海马区严重的神经元和细胞器超微病理改变,同时伴有神经突触可塑性变化,推测孕期铅暴露对子代学习记忆的损害与以上病理改变有关.     

两种方法建立多囊卵巢综合征大鼠模型的实验研究

目的:探讨脱氢表雄酮(DHEA)法与孕激素联合人绒毛膜促性腺激素(hCG)法建立的幼年雌性SD大鼠多囊卵巢综合征(PCOS)动物模型效果。方法:模型组Ⅰ44只SD大鼠用孕激素和hCG建模;模型组Ⅱ44只大鼠用DHEA建模,观察两组模型的稳态模型评估(HOMA)指数、其他主要指标及卵巢形态学改变,并与对照组Ⅰ、Ⅱ比较。结果:模型组Ⅰ和模型组Ⅱ失去规律动情周期的大鼠的比例分别为86.4和77.3;模型组Ⅱ体重低于对照组(P<0.05),血清E2高于对照组;两建模组大鼠血清睾酮、空腹血清胰岛素、空腹血糖和HOMA指数均高于对照组(P<0.05);两模型组大鼠卵巢均可见多个扩张的囊泡。结论:两法制作的PCOS大鼠模型均获得成功,孕激素联合hCG法更为理想。     

乙醇对实验大鼠精浆生化指标的相关性影响研究

目的：建立慢性饮酒实验大鼠模型,测定精浆生化（α-葡萄糖苷酶、酸性磷酸酶、精浆果糖、精浆锌）的含量变化,探讨不同酒精含量对大鼠精浆生化的影响。方法：将40只健康雄性成年SD大鼠随机分为四组,其中对照组给予蒸馏水灌胃,酒精组分别给予无水酒精0.5 g/（kg·d）、2.5 g/（kg·d）、5 g/（kg·d）灌胃,连续20周。测定各组实验大鼠精浆生化（α-葡萄糖苷酶、酸性磷酸酶、精浆果糖、精浆锌）的含量变化。结果：各酒精组实验大鼠精浆生化指标均明显低于正常对照组,差异均有统计学意义（P〈0.01）;而中、高剂量组实验大鼠精浆生化指标均明显低于低剂量组,差异均有统计学意义（P〈0.05或P〈0.01）。结论：酒精可影响雄性实验大鼠附属性腺的功能,导致雄性实验大鼠生殖系统损害,其中,中、高剂量乙醇的影响大于低剂量乙醇。     

宫内感染致肺损伤仔鼠血清IL-21与TNF-α及MMP-9表达水平

目的观察宫内感染引起的肺损伤仔鼠血清中白细胞介素-21(IL-21)、肿瘤坏死因子-α(TNF-α)和基质金属蛋白酶-9(MMP-9)的表达水平。方法选择健康的孕期SD大鼠,随机分为对照组和脂多糖(LPS)组,其中LPS组分为0.2、0.4、0.6、0.8、1.0、1.2 mg/kg 6个浓度组,分别在妊娠第18天腹腔注射不同浓度的LPS溶液,对照组腹腔注射同等体积的无菌生理盐水。记录孕期流产率及胎儿死亡率,通过苏木精-伊红染色观察新生仔鼠肺部组织的损伤情况,通过酶联免疫吸附试验(ELISA)检测新生仔鼠血清中IL-21、TNF-α和MMP-9的水平。结果与对照组相比,LPS组的新生仔鼠的肺部组织有明显的炎症损伤。与对照组相比,LPS组死亡率较高,差异具有统计学意义(P0.05),且LPS浓度升高,新生仔鼠的死亡率升高,各组间有统计学差异(P0.05)。LPS组的新生仔鼠血清中IL-21、TNF-α和MMP-9的水平高于对照组,差异具有统计学意义(P0.05)。且LPS浓度升高,IL-21、TNF-α和MMP-9的血清水平升高,各组间有统计学差异(P0.05)。结论通过对孕期大鼠腹腔注射LPS可成功建立宫内感染模型,孕期宫内感染会导致新生仔鼠死亡率升高,肺部组织损伤,同时LPS组的新生仔鼠血清中IL-21、TNF-α和MMP-9的表达水平增加,与LPS呈剂量依赖性。     

孕期铅暴露对子代大鼠海马区神经元超微结构及突触形态学影响的研究

【目的】 观察孕期铅暴露对子代大鼠脑海马区神经元、细胞器超微结构及神经突触形态学参数变化,探讨孕期铅暴露对子代大鼠学习记忆损害的可能机制。 【方法】 通过孕鼠自由饮用0.1%及0.2%醋酸铅溶液的方法建立模型,其雄性子代分别为低剂量铅暴露组(LG)及高剂量铅暴露组(HG),同时设立正常对照组(NG),每组9~12只大鼠。子代大鼠出生后36日龄应用透射电镜分别观察海马CA1区神经元、细胞器的病理超微结构改变和神经突触参数变化特征。 【结果】 铅暴露仔鼠脑海马区出现显著病理超微结构改变。HG组在神经元变性坏死、线粒体肿胀、内质网脱颗粒及高尔基体扩张等方面较对照组程度严重,差异有高度统计学意义(P<0.05或<0.01)。三组在突触后致密物质厚度、突触活性带长度、突触界面曲率及突触间隙等方面的差异有高度统计学意义(P均<0.01),提示铅暴露仔鼠脑海马CA1区突触后致密物质厚度减小、突触活性带长度缩短、突触界面曲率下降及突触间隙增宽。铅暴露组与对照组在突触数密度及面密度方面差异无统计学意义(P均>0.05)。 【结论】 孕期铅暴露可导致子代大鼠脑海马区严重的神经元和细胞器超微病理改变,同时伴有神经突触可塑性变化,推测孕期铅暴露对子代学习记忆的损害与以上病理改变有关。     

外源性甲状腺素对胎儿酒精效果大鼠背侧中缝核中5-羟色胺的影响

目的:研究胎儿酒精效果时大鼠背侧中缝核中5-羟色胺(5-HT)的变化以及外源性甲状腺素对其的影响。方法:实验于2006年1～7月在韩国朝鲜大学神经解剖实验室完成。选择SD母鼠36只,于怀孕第6天随机数字表法分为酒精组、正常对照组、酒精+甲状腺素组3个实验组和代理母组。酒精组每天摄取35 Cal的酒精;正常对照组每天摄取与酒精组相同热量的含糖奶粉;酒精+甲状腺素组每天摄取与酒精组同量的酒精,同时每天在颈后皮下注入5 mg/kg的T4;代理母组每天摄取正常的鼠食。酒精组、正常对照组、酒精+甲状腺素组母鼠分娩6 h后,与其子分开,麻醉后心脏采血,由韩国朝鲜大学医院检验室测试血液中酒精浓度和甲状腺素量,并以Kruskal-Wallistest分析。3组新生子鼠由代理母组的代理母鼠养育,并分别于生后0,7,14,21,28天(P0、P7、P14、P21、P28)时麻醉处死,采用免疫组化染色法,在脑干背侧中缝核中观察含有5-HT神经细胞的分布及形态。结果:①酒精组、酒精+甲状腺素组母鼠血液中酒精浓度高于正常对照组,差异显著(P<0.05)。酒精+甲状腺素组母鼠血液中甲状腺素含量高于酒精组,差异显著(P<0.05)。②酒精+甲状腺素组大鼠生后7天始出现分布和形态与正常对照组类似的成熟的含有5-HT神经细胞,即可观察到长而明显突起的、双极或多极的5-HT能神经元,生后14天始出现5-HT能神经元突起所形成的分支以及其相互间的连接。酒精组大鼠始终未出现具有上述表现的成熟的含有5-HT神经细胞。生后各年龄阶段背侧中缝核中,酒精组大鼠含有5-HT神经细胞数均较正常对照组明显减少,并在生后7天始出现的减少更明显。结论:孕期滥用酒精的母鼠接受外源性甲状腺素时,能促进其后代生后早期脑干背侧中缝核中5-HT的合成,促进含有5-HT能神经元的发育,进而能够改善胎儿酒精效果等降低甲状腺素所引起的脑发育障碍。     

Effects of pregnancy and progesterone on the consumption of ethanol by the high ethanol preferring (HEP) rat

A significant fraction of women continue to drink heavily during pregnancy, which is associated with the fetal alcohol syndrome, alcohol-related birth defects, alcohol-related neurodevelopmental disorder, and spontaneous abortion. The objective of this study was to determine whether the selectively bred genetic drinking Myers High Ethanol Preferring (HEP) rat would continue to drink through pregnancy. Rats from the F7 generation were screened by a 10-day 3-30% (v/v) ethanol concentration 'step up' procedure in order to determine the concentration which resulted in maximal drinking with an ethanol solution to total fluid ratio closest to 0.5. After baseline drinking of the preferred concentrations was established, female HEP rats were randomly selected for mating and their ethanol bottles were removed. Upon finding a 'sperm plug', male rats were removed and the ethanol was returned. A second group received injections of progesterone in sesame oil beginning with a 1.0 mg/kg/day dose which was increased to 3.0 mg/kg/day on gravid days (GD) 5-20. Vaginal smears confirmed that progesterone rendered the rats anoestrous. Neither pregnancy nor progesterone changed either the amount or proportion of ethanol consumed compared to the baseline period. The rats drank an average of 8.4 g/kg daily throughout pregnancy. A sharp drop in food intake was noted the day after mating. Beginning on GD 13, it was observed that pregnant rats showed a marked increase in the variance for proportion of ethanol consumed and body weight. Subsequently, only one of the eight impregnated rats successfully delivered a litter. The ethanol solution was removed and these rats mated again: seven of the eight rats delivered litters. These two findings suggest that the pregnant females must have begun to lose their litters on or after GD 13. Further, pregnancy does not affect the consumption of ethanol in the HEP rat. In addition, due to the fact that drinking by HEP rats during pregnancy leads to such a high rate of resorption of the fetus, this hybrid strain may also constitute a useful model for the study of alcohol-induced spontaneous abortion.     

Effects of prenatal ethanol exposure on iron utilization in the rat

The effects of prenatal ethanol exposure on iron metabolism in rat dams and pups were studied. Sperm-positive nulliparous dams were assigned to groups on the third day of gestation (G3): ET rats were fed a liquid diet containing 9% ethanol (v/v); PC rats were pair-fed a non-ethanol, isocaloric liquid diet; FC rats were fed the same nonethanol diet adlibitum. All animals were individually housed in stainless steel metabolic cages from G3 to G18 and transferred to polypropylene cages to await delivery. Food intake and dam body weight were significantly less in the ET and PC groups compared to the FC control group. Water intake was significantly greater in the ET dams than in controls. Gestation length was significantly increased in the ET rats only. Pup body weight was significantly decreased in the ET rats only compared to controls. Apparent absorption of iron in the ET dams was significantly greater than in the PC and FC dams. The inutero ethanol exposure resulted in a significant increase in liver and femur iron concentrations in the newborn pups when compared to the PC and FC control pups. The marked increase clue to understanding presence of liver pathology that has been reported to occur in children with fetal alcohol syndrome.     

Sex differences in pattern of drinking.

Drinking patterns of male and female Long-Evans rats were compared during a 15-day drinking period. All animals were tested for preference for alcohol for 24 h during which food, water, and beer containing 5% ethanol were freely available. Animals drinking 50 ml or more of beer were chosen for the experiments. On days 1-5, animals were offered food, water, and beer containing 5% ethanol (v/v). On days 6-15, the concentration of ethanol in the beer was doubled to 10% (v/v). Preference ratios (beer/total fluid) were higher for females than males, and females consumed more grams of alcohol per unit of body weight. When alcohol concentration was doubled, females increased alcohol intake (g/kg), while males tended to titrate alcohol intake to levels consumed at 5% concentration. Female patterns of drinking differed from male patterns of drinking.     

不同胎龄大鼠的组织铅分布

为研究不同胎龄胚胎／胎儿的组织铅分布规律,本研究用大鼠作动物模型,观察了４种染毒剂量下不同胎龄大鼠组织中的铅分布。将断乳２周的雌性Ｗｉｓｔａｒ大鼠１２０只,随机分为４组,分别饮含Ｐｂ２＋浓度为０、１０、５０和２００ｍｇ／Ｌ的饮水,１０周后与正常雄鼠交配,将各组孕鼠再随机分为４个亚组,于妊娠第１０、１４、１７、２０天时处死,测孕、胎鼠组织的铅含量。结果胎鼠脑铅含量随胎龄增长而增加,但脑铅浓度保持不变;胎鼠体铅含量随胎龄增长呈增加趋势,但胎龄１０天大鼠的体铅浓度高于１４天者。胎鼠体铅含量于妊娠后期较前期明显增加;胎鼠铅含量随胎龄的增加可能与妊娠后期胎鼠体内不断出现新的铅结合位点,特别是骨骼钙化有关。     

Effect of chronic ethanol administration on disposition of ethanol and its metabolites in rat.

We studied the effects of chronic alcohol intake on the disposition of alcohol and its metabolites in the rat. We used male Wistar rats for all of the experiments in this study. Using a pair-feeding process, rats were fed a liquid diet containing alcohol or without alcohol for 6 weeks. Ethanol solutions (0.5, 1.0, 1.5, and 2.0 g/kg body weight [BW]) were administered as a bolus, intravenously. We then measured blood ethanol and acetate concentrations. Simultaneous multiline fitting was performed using mean blood alcohol concentration (BAC)-time curves fitted to the one-compartment open model with parallel first-order and Michaelis-Menten elimination kinetics. At low doses (0.5, 1.0, and 1.5 g/kgBW), no differences were observed between the alcohol group and the control group with respect to ethanol elimination rate, area under the curve of ethanol (AUC(EtOH)), and mean residence time of ethanol (MRT(EtOH)). At higher doses (2.0 g/kgBW), ethanol elimination rate in the alcohol group was significantly higher than in the control group (P<.5%). These findings were also substantiated by corresponding changes in AUC(EtOH) and MRT(EtOH). At low doses, no differences were observed between the alcohol group and the control group with respect to plateau concentration of acetate (AcT) (concentration of steady state=C(ss)AcT), area under the curve of AcT (AUC(AcT)), and mean residence time of AcT (MRT(AcT)). However, at higher doses, although there were no differences in C(ss)AcT, both AUC(AcT) and MRT(AcT) were significantly lower in the alcohol group when compared to the control group (P<.5%). Chronic alcohol consumption increases ethanol oxidation and AcT metabolism in rats, as observed at high blood alcohol concentrations (BACs). These effects were observed at BACs of 3.5-4.5 mg/ml, and were not observed at lower doses. Thus, with general alcohol consumption, interindividual differences and intra-individual changes in alcohol metabolism may not take into account increased or accelerated metabolism due to alcohol tolerance.     

Acetaldehyde and alcohol levels in pregnant rats and their fetuses

Alcohol and acetaldehyde blood levels were measured in chronic alcoholic pregnant rats and their fetuses at 15, 19 and 21 days of gestation. Similar ethanol concentrations were found in fetal and maternal blood in all gestation periods studied, however levels in amniotic fluid were higher than in mother's blood, especially in the early stages of gestation. Acetaldehyde concentrations were always lower in fetal than in maternal blood although increasing throughout gestation. The levels in fetal blood and amniotic fluid compared to maternal blood, were ca. 40, 50 and 70% at 15, 19 and 21 days of gestation, respectively; those for the placenta and fetal tissues were lower, i.e., 25, 40 and 50%. Similar alcohol and acetaldehyde ratios (fetus/mother's concentration) were obtained when pregnant non-alcoholic rats were administered cyanamide and ethanol (2 g/kg) at 11, 15, 19 and 21 days of gestation. These results demonstrate that ethanol freely crosses the placental barrier, but there is a concentration gradient of acetaldehyde between mother and fetus which varies with gestation age.     

Volitional consumption of ethanol by fawn-hooded rats: Effects of alternative solutions and drug treatments

Behavioral and neurochemical measures of brain 5-hydroxytryptamine (5-HT) function in the Fawn-Hooded rat are abnormal relative to outbred strains of rats. Fawn-Hooded rats freely drink large amounts of 10% ethanol in the presence of water and have been proposed to be an animal model for studies related to alcoholism. In this study, Fawn-Hooded rats were given solutions of ethanol increasing in concentration from 3% to 30% (w/v in tap water) over 10 days with tap water in a second drinking tube and a third tube left empty. The solutions of ethanol that produced maximal drinking with a preference (ml ethanol/ml total fluid) near 50% ranged from 5% to 13%, which became: the fixed individual concentrations for each rat. After a 5-day baseline period the rats were offered a solution in the third drinking tube of either 0.5% aspartame or chocolate Ultra SlimFast (diluted with water 2: 1). The chocolate drink, but not aspartame, significantly reduced the consumption of alcohol by 73%. For the drug experiments, the rats were given successive 4-day periods of: baseline drinking; drug or saline injections b.i.d.; and a posttreatment period. Neither ipsapirone, a 5-HT_1a partial agonist, nor naltrexone injected inhibited the intakes of ethanol solutions. Treatment with 2.5 mg/kg of amperozide, a 5-HT₂ antagonist, decreased the consumption of ethanol by 38%, but also caused a decrease in consumption of food. These results show a pattern of drinking of increasing concentrations of ethanol different than other strains of rats. Because ethanol intakes of the Fawn-Hooded rat decline precipitously when offered palatable chocolate drink and fail to respond to drugs known to decrease human ethanol intake, this strain may not be a valid model for testing the effects of centrally acting drugs on the consumption of ethanol.     

The Fetal Alcohol Syndrome And Placental Transport Of Valine

Ingestion of ethanol inhibits placental uptake and transfer of valine to the rat fetus and may be contributory to the impaired fetal growth and dysgenesis associated with the fetal alcohol syndrome.     

Prenatal ethanol exposure decreases hippocampal NMDA-sensitive [3H]-glutamate binding site density in 45-day-old rats.

The effect of prenatal ethanol exposure on N-methyl-D-aspartate (NMDA)-sensitive [3H]-glutamate receptor binding site density was studied in rat brain. Pregnant Sprague-Dawley rats were fed a liquid diet containing 3.35% ethanol throughout gestation. This diet produced maternal peak blood ethanol levels of about 39 mg/dl eight hours after the administration of the liquid diet. Pair-fed dams received an isocalorically matched liquid diet and an ad lib lab chow group served as control for the paired feeding technique. At 45 days of age, offspring from each of the three diet groups were sacrificed and brain NMDA-sensitive [3H]-glutamate binding site density measured using in vitro radiohistochemical techniques. NMDA-sensitive [3H]-glutamate binding site density was reduced significantly by 19 to 29% in the apical dendritic field regions of dentate gyrus, hippocampal CA1 and subiculum of dorsal hippocampal formation of fetal alcohol rats compared to pair-fed and ad lib controls. NMDA-sensitive [3H]-glutamate binding site density was not significantly different among the three groups in the ventral hippocampal formation, posterior neocortex, lateral entorhinal cortex or cerebellum. These results are consistent with our previous observations of a reduction in total [3H]-glutamate receptor binding site density in the dorsal hippocampal formation of fetal alcohol rats, as well as more recent electrophysiological observations of a decrease in the sensitivity of fetal alcohol hippocampal slices to NMDA.     

ETHANOL ELIMINATION IN ALCOHOL-TREATED PREGNANT RATS

The effects of chronic intake of alcohol on ethanol eliminationwere studied in 20-day pregnant rats, in their foetuses, andin virgin rats. Experimental animals received ethanol in drinkingwater (from 10% to 25% in 2 months) (alcohol group), whereascontrols drank only water. At the end of chronic exposure, alcoholdehydrogenase activity was determined in stomach and liver andcytochronse P-450 was measured in liver. In a complementaryassay, the same experimental groups of rats were given an acutedose of ethanol (2 g/kg body wt, 25% w/v) either intragastricallyor intraperitoneally, at the end of the chronic exposure, todetermine first-pass ethanol metabolism and pharmacokineticparameters of its elimination. Significant differences werefound between alcohol and control groups for liver and stomachalcohol dehydrogenase activity in pregnant rats. Only in virginsdid chronic alcohol treatment significantly increase the livercytochrome P-450 content. In virgin rats, the first-pass metabolismof ethanol was lower in the alcohol group than in control. Bycontrast, in control rats, the first-pass of ethanol was lowerin pregnant, than in virgin, rats. The metabolic rate of ethanolelimination (mg/kg body wt/hr) was clearly enhanced in alcoholicvirgin rats, demonstrating that this model of chronic alcoholisminduces metabolic tolerance to ethanol. In alcoholic pregnantrats, a surprisingly low theoretical volwne of body ethanoldistribution (55 ml/100 g body wt vs. 80 ml/100 g body wt inthe other groups) masked their metabolic tolerance to ethanol.This preliminary study should be taken into account when evaluatingthe effects of chronic or/and acute alcohol intake during pregnancyon the circulating ethanol levels in foetuses and on futuredevelopment of the foetal alcohol syndrome.