Research & Development Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI, 48201, United States; Department of Neurosurgery, Wayne State University School of Medicine, 4160 John R St., Detroit, MI, 48201, United States.
Research & Development Service, John D. Dingell VA Medical Center, 4646 John R St., Detroit, MI, 48201, United States; Department of Neurosurgery, Wayne State University School of Medicine, 4160 John R St., Detroit, MI, 48201, United States.
Alcohol. 2019 Sep;79:17-24. doi: 10.1016/j.alcohol.2018.10.011. Epub 2018 Oct 29.
Individuals fetally exposed to alcohol have a disproportionate risk for developing lifetime alcohol dependence, an association that may be confounded by the presence of comorbid conditions, such as anxiety. Anxiety is also observed following fetal alcohol exposure and is known to exacerbate ethanol consumption, highlighting the utility of animal models to assess this relationship. The present study evaluated the impact of third-trimester equivalent ethanol exposure on ethanol consumption and anxiety-like, marble burying behavior in adult, male C57BL/6 mice following exposure to chronic intermittent ethanol vapor, proposed to model dependence. Neonatal mice (P5-6, 2.5-3.0 g) were administered one injection of saline or ethanol (2.5 g/kg, subcutaneously [s.c.]). Pre-vapor marble burying and limited-access two-bottle choice ethanol intake (15% v/v, 2 h) were comparable in adults (8 weeks of age) across neonatal treatment groups. Five consecutive drinking sessions were repeated 72 h after each weekly ethanol vapor exposure procedure for a total of five vapor/drinking cycles. Consistent with prior research, an increase in voluntary ethanol drinking was observed in vapor-exposed, neonatal saline-treated mice throughout the study starting after the second vapor cycle compared to both air-exposed control groups. In neonatal ethanol-treated mice, this increase in ethanol intake and preference following vapor exposure was accelerated, being observed after the first vapor cycle, and observed at an augmented level compared to vapor-exposed, neonatal saline-treated mice and air controls for both neonatal conditions. Conversely, marble burying was enhanced equivalently in vapor-exposed mice from either neonatal treatment group relative to their respective air-exposed controls. These data recapitulate clinical observations of enhanced sensitivity for alcohol dependence following developmental alcohol exposure, which may reflect enhanced motivational drive rather than potentiated negative affect. The present model will facilitate the future exploration of mechanisms that underlie increased risk for alcohol use after early developmental exposure.
胎儿期暴露于酒精的个体患终身酒精依赖的风险不成比例，这种关联可能因焦虑等合并症的存在而混淆。在胎儿酒精暴露后也会观察到焦虑，并且已知焦虑会加剧乙醇的消耗，这突出了动物模型在评估这种关系方面的效用。本研究评估了在暴露于慢性间歇性乙醇蒸气后，相当于妊娠晚期的乙醇暴露对成年雄性 C57BL/6 小鼠乙醇消耗和焦虑样、大理石掩埋行为的影响，该模型拟模拟依赖性。新生小鼠（P5-6，2.5-3.0g）接受一次生理盐水或乙醇（2.5g/kg，皮下[s.c.]）注射。在成年期（8 周龄），跨越新生治疗组，预蒸气大理石掩埋和有限接入双瓶选择乙醇摄入（15%v/v，2h）是可比的。在每次每周乙醇蒸气暴露程序后，连续进行五次饮用会议，总共进行五次蒸气/饮用周期。与先前的研究一致，在整个研究中，从第二次蒸气周期开始，暴露于蒸气的新生盐水处理小鼠的自愿乙醇饮用量增加，与空气暴露的对照组相比。在新生乙醇处理的小鼠中，这种暴露于蒸气后乙醇摄入和偏好的增加被加速，在第一次蒸气周期后观察到，并且与暴露于蒸气的新生盐水处理小鼠和空气对照组相比，在两种新生条件下观察到增强的水平。相反，暴露于蒸气的小鼠中的大理石掩埋相对于各自的空气暴露对照组同样增强。这些数据再现了临床观察到的发育性酒精暴露后酒精依赖敏感性增加，这可能反映了增强的动机驱动而不是增强的负性情绪。本模型将促进未来对早期发育暴露后增加酒精使用风险的机制的探索。
