Adolescent alcohol exposure is associated with lasting behavioral changes in humans and in mice. Prior work from our laboratory and others have demonstrated that C57BL/6J and DBA/2J mice differ in sensitivity to some effects of acute alcohol exposure during adolescence and adulthood. However, it is unknown if these strains differ in cognitive, anxiety-related, and addiction-related long-term consequences of adolescent intermittent alcohol exposure. This study examined the impact of a previously validated adolescent alcohol exposure paradigm (2–3 g/kg, i.p., every other day PND 30–44) in C57BL/6J and DBA/2J male and female mice on adult fear conditioning, anxiety-related behavior (elevated plus maze), and addiction-related phenotypes including nicotine sensitivity (hypothermia and locomotor depression) and alcohol sensitivity (loss of righting reflex; LORR). Both shared and strain-specific long-term consequences of adolescent alcohol exposure were found. Most notably, we found a strain-specific alcohol-induced increase in sensitivity to nicotine's hypothermic effects during adulthood in the DBA/2J strain but not in the C57BL/6J strain. Conversely, both strains demonstrated a robust increased latency to LORR during adulthood after adolescent alcohol exposure. Thus, we observed strain-dependent cross-sensitization to nicotine and strain-independent tolerance to alcohol due to adolescent alcohol exposure. Several strain and sex differences independent of adolescent alcohol treatment were also observed. These include increased sensitivity to nicotine-induced hypothermia in the C57BL/6J strain relative to the DBA/2J strain, in addition to DBA/2J mice showing more anxiety-like behaviors in the elevated plus maze relative to the C57BL/6J strain. Overall, these results suggest that adolescent alcohol exposure results in altered adult sensitivity to nicotine and alcohol with some phenotypes mediated by genetic background.

青少年酒精暴露与人类和小鼠的持久行为变化有关。我们实验室和其他实验室的先前工作表明，C57BL/6J 和 DBA/2J 小鼠对青春期和成年期间急性酒精暴露的某些影响的敏感性不同。然而，目前尚不清楚这些菌株在青少年间歇性酒精暴露的认知、焦虑相关和成瘾相关的长期后果方面是否存在差异。这项研究在 C57BL/6J 和 DBA/2J 雄性和雌性小鼠中检验了先前验证的青少年酒精暴露模式（2-3 g/kg，ip，每隔一天 PND 30-44）对成年恐惧条件反射、焦虑-相关行为（高架十字迷宫）和成瘾相关表型，包括尼古丁敏感性（体温过低和运动抑制）和酒精敏感性（翻正反射丧失；LORR）。发现了青少年酒精暴露的共同的和特定的长期后果。最值得注意的是，我们发现 DBA/2J 品系在成年期会出现特定品系酒精诱导的对尼古丁低温效应的敏感性增加，但在 C57BL/6J 品系中则不然。相反，在青少年酒精暴露后，这两种菌株在成年期都表现出 LORR 潜伏期的显着增加。因此，我们观察到青少年酒精暴露导致对尼古丁的菌株依赖性交叉过敏和对酒精的菌株独立耐受性。还观察到一些与青少年酒精治疗无关的菌株和性别差异。这些包括相对于 DBA/2J 品系，C57BL/6J 品系对尼古丁诱导的低温的敏感性增加，此外，相对于 C57BL/6J 品系，DBA/2J 小鼠在高架十字迷宫中表现出更多的焦虑样行为。总体而言，这些结果表明青少年酒精暴露会导致成人对尼古丁和酒精的敏感性改变，并具有一些由遗传背景介导的表型。