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.
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|Linsenbardt, David N; Moore, Eileen M; Griffin, Kevar D et al. (2011) Tolerance to ethanol's ataxic effects and alterations in ethanol-induced locomotion following repeated binge-like ethanol intake using the DID model. Alcohol Clin Exp Res 35:1246-55|
|Moore, Eileen M; Mariani, John N; Linsenbardt, David N et al. (2010) Adolescent C57BL/6J (but not DBA/2J) mice consume greater amounts of limited-access ethanol compared to adults and display continued elevated ethanol intake into adulthood. Alcohol Clin Exp Res 34:734-42|