Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Addict Biol. 2021 May;26(3):e12965. doi: 10.1111/adb.12965. Epub 2020 Oct 5.
Alcohol abuse and dependence are world-wide health problems. Most research on alcohol use focuses on the consequences of moderate to high levels of alcohol. However, even at low concentrations, alcohol is capable of producing effects in the brain that can ultimately affect behavior. The current studies seek to understand the effects of low-dose alcohol (blood alcohol levels of ≤10mM). To do so, these experiments utilize a combination of behavioral and molecular techniques to (1) assess the ability of the interoceptive effects of a low dose of alcohol to gain control over goal-tracking behavior in a Pavlovian discrimination task, (2) determine brain regional differences in cellular activity via expression of immediate early genes (IEGs), and (3) assess the role of the dentate gyrus in modulating sensitivity to the interoceptive effects of a low dose of alcohol. Here, we show that intragastric administration of a dose of 0.8 g/kg alcohol produces blood alcohol levels ≤10mM in both male and female Long-Evans rats and can readily be trained as a Pavlovian interoceptive drug cue. In rats trained on this procedure, this dose of alcohol also modulates expression of the IEGs c-Fos and Arc in brain regions known to modulate expression of alcohol interoceptive effects. Finally, pharmacological inactivation of the dentate gyrus with GABA agonists baclofen and muscimol disrupted the ability of a low dose of alcohol to serve as an interoceptive cue. Together, these findings demonstrate behavioral and molecular consequences of low-dose alcohol.
酗酒和依赖是全球性的健康问题。大多数关于酒精使用的研究都集中在中等到高水平的酒精所带来的后果上。然而，即使在低浓度下，酒精也能够对大脑产生影响，最终影响行为。目前的研究旨在了解低剂量酒精（血液酒精浓度≤10mM）的影响。为此，这些实验结合了行为和分子技术，以（1）评估低剂量酒精的内感受效应在巴甫洛夫辨别任务中控制目标跟踪行为的能力，（2）通过即时早期基因（IEGs）的表达确定大脑区域的细胞活动差异，以及（3）评估齿状回在调节对低剂量酒精内感受效应的敏感性中的作用。在这里，我们表明，给雄性和雌性 Long-Evans 大鼠灌胃 0.8g/kg 的酒精剂量可产生血液酒精浓度≤10mM，并且可以很容易地作为一种巴甫洛夫内感受药物线索进行训练。在接受这种程序训练的大鼠中，这种剂量的酒精也会调节已知调节酒精内感受效应表达的大脑区域中 IEGs c-Fos 和 Arc 的表达。最后，用 GABA 激动剂巴氯芬和 muscimol 使齿状回失活破坏了低剂量酒精作为内感受线索的能力。总之，这些发现表明了低剂量酒精的行为和分子后果。
