Effects of periadolescent ethanol exposure on alcohol preference in two BALB substrains

Effects of periadolescent ethanol exposure on alcohol preference in two BALB substrains
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DOI:
10.1016/j.alcohol.2004.08.007
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发表时间:
2004-10-01
期刊:
影响因子:
2.3
通讯作者:
McClearn, GE
McClearn, GE
中科院分区:
医学4区
文献类型:
--
作者:
Blizard, DA;Vandenbergh, DJ;McClearn, GE

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在许多社会中,在青春期接触酒精是一种成年仪式,但只有一部分接触酒精的人会对酒精产生依赖。为了探索个体对酒精暴露的反应差异,我们在动物模型中比较了青春期酒精暴露对饮酒的影响。从第6周到第12周,两个BALB亚系的雄性和雌性小鼠被暴露于三种形式的乙醇中的一种-选择[水对10%(体积/体积)乙醇]、强迫(单瓶10%乙醇)或渐进(单瓶暴露,从0.5%乙醇开始,每隔2天增加到10%乙醇),然后立即进行两瓶酒精偏好测试(10%乙醇对水),持续15天。所有三种形式的酒精暴露都增加了BALB/cByJ雄性和雌性BALB/cByJ小鼠的酒精偏好,与未接触酒精的对照动物的研究结果相比。在BALB/CJ小鼠中,只有逐渐的酒精暴露才能增加对酒精的偏好。在逐步酒精暴露组小鼠的延长酒精偏好测试中(总共39天),逐步酒精暴露的BALB/cByJ雄性小鼠的酒精偏好较高,但对照组雌性小鼠对该品系的酒精偏好-以前是乙醇幼稚的,但在这一点上已经在两瓶模式中接受了10%的乙醇15d-上升到逐步酒精暴露组雌性小鼠的酒精偏好水平。这一发现表明,青少年和成年酒精暴露都刺激了这种品系的雌性小鼠的酒精偏好。在成年后的几天测试中,逐渐暴露于乙醇的BALB/CJ小鼠的酒精偏好下降,导致在延长测试期间,逐渐暴露于乙醇对该品系雄性和雌性小鼠的酒精偏好都没有影响。这些品系差异支持了酒精暴露对酒精偏好的影响的遗传基础,并符合一系列文献,表明在遗传未定义的大鼠中酒精暴露的影响存在显著的个体差异,以及近交系大鼠对酒精暴露的反应存在差异。在小鼠模型中探索这种基因与环境相互作用的机制可能有助于阐明酒精暴露对人类影响的个体差异,并有助于理解酒精中毒的原因。(C)2005 Elsevier Inc.保留所有权利。
Ethanol exposure during adolescence is a rite of passage in many societies, but only a subset of individuals exposed to ethanol becomes dependent on alcohol. To explore individual differences in response to ethanol exposure, we compared the effects of periadolescent ethanol exposure on alcohol drinking in an animal model. Male and female mice of two BALB substrains were exposed to ethanol in one of three forms-choice [water vs. 10% (volume/volume) ethanol], forced (10% ethanol in a single bottle), or gradual (single bottle exposure, starting with 0.5% ethanol and increasing at 2-day intervals to 10% ethanol)-from the 6th through the 12th week of age and administered two-bottle alcohol preference tests (10% ethanol vs. water) for 15 days immediately thereafter. All three forms of ethanol exposure increased alcohol preference in male and female BALB/cByJ mice, relative to findings for ethanol-naive control animals. Only gradual ethanol exposure produced an increase in alcohol preference in BALB/cJ mice. During extended alcohol preference testing (for a total of 39 days) of mice in the gradual ethanol exposure group, the higher alcohol preference of the gradual ethanol-exposed BALB/cByJ male mice persisted, but alcohol preference of control group female mice in this strain-formerly ethanol naive, but at this point having received 10% ethanol in the two-bottle paradigm for 15 days-rose to the level of alcohol preference of female mice in the gradual ethanol exposure group. This finding demonstrated that both adolescent and adult ethanol exposure stimulated alcohol preference in female mice of this strain. Across days of testing in adulthood, alcohol preference of the,gradual ethanol-exposed BALB/cJ mice decreased, resulting in a lack of effect of gradual exposure to ethanol on alcohol preference in both male and female mice of this strain during the period of extended testing. These strain differences support a genetic basis for the effects of ethanol exposure on alcohol preference and fit within a body of literature, showing substantial individual differences in the effects of ethanol exposure among genetically undefined rats and differences in response to ethanol exposure among inbred rat strains. Exploration of the mechanisms underlying this gene by environment interaction in a mouse model may help elucidate individual differences in the effects of ethanol exposure in human beings and contribute to the understanding of the causes of alcoholism. (c) 2005 Elsevier Inc. All rights reserved.