Alcohol intake and aversion during adolescence in 8 inbred mouse strains

描述（由申请人提供）：在青春期早期（14岁之前）开始饮酒与酒精依赖终生患病率的增加有关（Grant & Dawson，1997）。未来酗酒的风险也随着酗酒家族史的增加而增加（Schuckit & Smith，1996）。然而，为了充分了解青少年暴露于乙醇的影响和与酒精中毒相关的遗传因素，使用动物模型是必要的。拟议的研究将检查：成年和青春期小鼠之间乙醇摄入量的差异，以及8个近交系小鼠品系中先前在青春期或成年期暴露于乙醇的成年小鼠之间饮酒的差异（Aim 1）;青少年条件性味觉厌恶（CTA）的诱导程度以及先前乙醇暴露的程度在相同的8个近交系小鼠品系中，酒精摄入量（在青春期或成年期）改变了成年期对酒精厌恶性质的敏感性（目的2），最后，在8个近交系小鼠品系中，酒精摄入量和青春期和成年期对酒精的CTA的程度将相关。男性青少年（早期：P28-32和晚期：将C57 BL/6 J、DBA/2 J、129 S1/SvlmJ、A/J、BALB/cByJ、BTBR T+tf/tf、C3 H/HeJ和FVB/NJ近交系小鼠的成年（P38-42）和成年（P70-74）小鼠每天给予20%（v/v）乙醇溶液2小时，连续5天。然后，在完成初始乙醇暴露后37天，当青少年达到成年年龄时，重新评估小鼠的乙醇摄入量（目标1）。接下来，雄性青春期和成年小鼠（相同基因型和年龄范围）将被给予10%（w/v）的糖-水溶液1小时，并且在糖-水溶液后立即腹膜内（ip）注射盐水或乙醇（2或4 g/kg）以产生乙醇诱导的促味剂CTA。小鼠将接受该促味剂/乙醇配对3次，在每次糖-水接触/乙醇注射处理之间恢复一天。同样，在37天禁欲期后，动物将在成年期再次暴露于CTA程序，这次使用不同的促味剂（0.05%氯化钠），以确定青春期之前的乙醇处理是否会改变成年期对乙醇厌恶性质的敏感性（目的2）。最后，对于青少年和成年小鼠，乙醇饮用和CTA表型将在基因型之间相关。这项工作将检查两个发展暴露/敏感性乙醇以及乙醇摄入量/敏感性的差异，由于基因型;检查这两种影响一起可能会产生重要的和有趣的相互作用，这可能会导致更好地了解酒精使用和滥用从青春期到成年期的人类。

DESCRIPTION (provided by applicant): Initiation of alcohol consumption during early adolescence (before age 14) is related to an increase in lifetime prevalence of alcohol dependency (Grant & Dawson, 1997). The risk for future alcoholism also increases with a positive family history of alcohol abuse (Schuckit & Smith, 1996). However, in order to fully understand the impact of adolescent exposure to ethanol and the genetic factors associated with alcoholism, use of animal models are necessary. The proposed research will examine: differences in ethanol intake between adult and adolescent mice, as well as the differences in drinking between adult mice that were either previously exposed to ethanol during adolescence or adulthood in 8 inbred mouse strains (Aim 1); the extent to which a conditioned taste aversion (CTA) can be induced in adolescents as well as the degree to which prior ethanol exposure (either in adolescence or adulthood) alters sensitivity to the aversive properties of alcohol in adulthood in the same 8 inbred mouse strains (Aim 2) and lastly, the extent to which alcohol intake and CTA to alcohol in adolescence and adulthood will correlate across the 8 inbred mouse strains. Male adolescent (early: P28-32 and late: P38-42) and-adult (P70-74) mice ofthe C57BL/6J, DBA/2J, 129S1/SvlmJ, A/J, BALB/cByJ, BTBR T+tf/tf, C3H/HeJ, and FVB/NJ inbred strains will be given access to a 20% (v/v) ethanol solution for 2-h a day, for 5 consecutive days. Mice will then be reassessed for ethanol intake, 37 days after the completion of the initial ethanol exposure, when the adolescents reach adult-age (Aim 1). Next, male adolescent and adult mice (ofthe same genotypes and age-ranges) will be given access to a 10% (w/v) sugar-water solution for 1-h, and immediately after sugar-water access mice will be intraperitoneally (ip) injected with saline or ethanol (2 or 4 g/kg) to produce an ethanol-induced CTA to the tastant. Mice will receive this tastant/ethanol pairing 3 times, with one day of recovery between each sugar-water access/ethanol injection treatment. Again, after a 37 day abstinence period animals will be re- exposed to the CTA procedure in adulthood, this time using a different tastant (0.05% sodium-chloride) to determine whether previous ethanol treatment in adolescence will alter adult sensitivity to the aversive properties of ethanol (Aim 2). Lastly, ethanol drinking and CTA phenotypes will be correlated across genotypes for both adolescent and adult mice. This work will examine both developmental exposure/sensitivity to ethanol as well as differences in ethanol intake/sensitivity due to genotype; examining both of these influences together may yield important and interesting interactions which could result in a greater understanding of alcohol use and abuse from adolescence into adulthood in humans.