Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, 11364, Stockholm, Sweden.
Center for Molecular Medicine, L8:00, Karolinska University Hospital, 17176, Stockholm, Sweden.
Sci Rep. 2021 Jun 4;11(1):11856. doi: 10.1038/s41598-021-91215-1.
Alcohol use disorders (AUD) often co-occur with anxiety and depressive disorders, and anxiety often drives relapse during alcohol abstinence. Optimal AUD pharmacotherapies may thus need to target both excessive alcohol intake and elevated anxiety. (-)-OSU6162 (OSU) is a monoamine stabilizer that attenuates alcohol-mediated behaviors in both preclinical and clinical settings. However, OSU's effect on anxiety-like behavior following long-term drinking remains unknown. To this end, we utilized a genetic rat model that exhibits increased anxiety- and depression-like behaviors (Flinders Sensitive Line; FSL) and their controls (Flinders Resistant Line; FRL). Using the novelty suppressed feeding (NSF) test, we evaluated anxiety-like behaviors (1) at baseline, (2) following long-term voluntary drinking and after 24 h of alcohol deprivation, and (3) following OSU administration in the same animals. At baseline, FSL animals displayed significantly elevated anxiety-like characteristics compared to FRL. Compared to alcohol-naïve animals, long-term drinking significantly reduced anxiety-like behaviors in FSL, without any significant effects in FRL animals. Compared to vehicle, OSU administration significantly reduced anxiety-like behaviors in alcohol-naïve FSL and long-term drinking FRL animals. While there was no significant difference in alcohol intake between FSL and FRL, OSU attenuated alcohol intake in both strains. Conclusively, in addition to the compound's previously identified ability to suppress alcohol-mediated behaviors, OSU may also possess anxiolytic properties, warranting further clinical evaluation in both AUD and anxiety disorder settings.
酒精使用障碍（AUD）常与焦虑和抑郁障碍共病，且焦虑常导致酒精戒断期间的复发。因此，最佳的 AUD 药物治疗可能需要同时针对过度饮酒和升高的焦虑。(-)-OSU6162（OSU）是一种单胺稳定剂，可在临床前和临床环境中减轻酒精介导的行为。然而，OSU 对长期饮酒后焦虑样行为的影响尚不清楚。为此，我们利用一种遗传大鼠模型，该模型表现出增加的焦虑和抑郁样行为（弗林德斯敏感系；FSL）及其对照（弗林德斯抗性系；FRL）。使用新颖性抑制摄食（NSF）测试，我们评估了焦虑样行为（1）在基线时，（2）在长期自愿饮酒后和酒精剥夺 24 小时后，以及（3）在相同动物中给予 OSU 后。在基线时，FSL 动物与 FRL 相比表现出明显升高的焦虑样特征。与酒精-naïve 动物相比，长期饮酒显著降低了 FSL 的焦虑样行为，而 FRL 动物则没有显著影响。与载体相比，OSU 在酒精-naïve FSL 和长期饮酒 FRL 动物中显著降低了焦虑样行为。尽管 FSL 和 FRL 之间的酒精摄入量没有显著差异，但 OSU 减轻了两种品系的酒精摄入量。总之，除了该化合物先前被确定的抑制酒精介导行为的能力外，OSU 还可能具有抗焦虑特性，值得在 AUD 和焦虑障碍环境中进一步进行临床评估。
