Department of Psychiatry, Indiana University School of Medicine, 320 W. 15th Street, NB 300E, Indianapolis, IN, 46202, USA.
Sci Rep. 2024 Jun 18;14(1):14029. doi: 10.1038/s41598-024-64565-9.
Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
binge 饮酒（BD）是导致酒精使用障碍危害的主要因素。大多数啮齿动物模型不会导致 binge 水平的血液酒精浓度（BAC），为了更好地理解与 BD 相关的神经生物学机制中的个体和性别差异，使用杂交大鼠品系将是有价值的。在这里，我们开发了一种新的 BD 模型，在经过 3 个多月的间歇性接触 20%酒精后，Wistar 大鼠每周两次进行 5 分钟的摄入（我们称之为 Two-shot），两次摄入之间有 10 分钟的休息。我们的研究结果表明，在 Two-Shot 期间，大多数动物达到了≥80mg% BAC 水平（当短暂禁食时）。然而，当将酒精浓度从 20%增加到 30%、40%或 50%时，大鼠的摄入量达到相似水平，这表明即使在前端加载时，它们也能快速感知酒精的影响。纳曲酮（1mg/kg）降低了两性的 Two-Shot 饮酒量，验证了临床治疗人类问题饮酒的药物对摄入的抑制作用。此外，普萘洛尔（β-肾上腺素能受体拮抗剂）和特拉唑嗪（α1-肾上腺素能受体拮抗剂）降低了雌性但不降低雄性的 BD，在较低剂量下也是如此。因此，我们的结果为杂交大鼠的 BD 提供了一种新模型，并表明雌性 binge 对肾上腺素能调节更为敏感，这可能为提供一种新的性别相关治疗方法。
