Beeler Erik, Nobile Zachary L, Homanics Gregg E
Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, 6068 Biomedical Science Tower-3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA.
Brain Sci. 2019 Mar 6;9(3):56. doi: 10.3390/brainsci9030056.
Alcohol use disorder is a devastating disease with a complex etiology. Recent preclinical studies have revealed that paternal preconception chronic intermittent ethanol (EtOH) exposure via vaporized EtOH altered drinking behaviors and sensitivity to EtOH selectively in male offspring. In the current study, we used a voluntary oral route of paternal preconception EtOH exposure, i.e., intermittent every-other-day two-bottle choice drinking, and tested offspring for behavioral alterations. Fifteen EtOH drinking sires and 10 control sires were mated to EtOH naïve females to produce EtOH-sired and control-sired offspring. These offspring were tested using the elevated plus maze, open field, drinking in the dark, and unlimited access two-bottle choice assays. We found that paternal preconception every-other-day two-bottle choice drinking resulted in reduced EtOH consumption selectively in male offspring in the drinking in the dark assay compared to control-sired offspring. No differences were detected in either sex in the unlimited access two-bottle choice and elevated plus maze assays. Open field analysis revealed complex changes in basal behavior and EtOH-induced behaviors that were sex specific. We concluded that paternal preconception voluntary EtOH consumption has persistent effects that impact the next generation. This study adds to a growing appreciation that one's behavioral response to EtOH and EtOH drinking behavior are impacted by EtOH exposure of the prior generation.
酒精使用障碍是一种病因复杂的毁灭性疾病。最近的临床前研究表明，父代受孕前通过汽化乙醇进行慢性间歇性乙醇（EtOH）暴露会改变雄性后代的饮酒行为和对乙醇的敏感性。在本研究中，我们采用父代受孕前乙醇暴露的自愿口服途径，即每隔一天进行两瓶选择的间歇性饮酒，并测试后代的行为改变。15只饮酒的父代与10只对照父代与未接触过乙醇的雌性交配，以产生乙醇暴露父代和对照父代的后代。这些后代使用高架十字迷宫、旷场、暗箱饮酒和无限制两瓶选择试验进行测试。我们发现，与对照父代的后代相比，父代受孕前每隔一天进行两瓶选择饮酒导致雄性后代在暗箱饮酒试验中乙醇摄入量选择性降低。在无限制两瓶选择和高架十字迷宫试验中，未检测到两性之间的差异。旷场分析揭示了基础行为和乙醇诱导行为的复杂变化，这些变化具有性别特异性。我们得出结论，父代受孕前自愿摄入乙醇具有影响下一代的持续效应。这项研究进一步证明，一个人对乙醇的行为反应和饮酒行为会受到上一代乙醇暴露的影响。
