Alper Kenneth, Dong Bin, Shah Relish, Sershen Henry, Vinod K Yaragudri
Department of Psychiatry, New York University School of Medicine, New York, NY, United States.
Department of Neurology, New York University School of Medicine, New York, NY, United States.
Front Pharmacol. 2018 Aug 31;9:994. doi: 10.3389/fphar.2018.00994. eCollection 2018.
There is a substantive clinical literature on classical hallucinogens, most commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use disorder. However, there has been no published research on the effect of LSD on alcohol consumption in animals. This study evaluated the effect of LSD in mice using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice were exposed to ethanol to develop preference and divided into three groups of equal ethanol consumption, and then treated with single intraperitoneal injection of saline or 25 or 50 μg/kg LSD and offered water and 20% ethanol. The respective LSD-treated groups were compared to the control group utilizing a multilevel model for repeated measures. In mice treated with 50 μg/kg LSD ethanol consumption was reduced relative to controls ( = 0.0035), as was ethanol preference ( = 0.0024), with a group mean reduction of ethanol consumption of 17.9% sustained over an interval of 46 days following LSD administration. No significant effects on ethanol consumption or preference were observed in mice treated with 25 μg/kg LSD. Neither total fluid intake nor locomotor activity in the LSD-treated groups differed significantly from controls. These results suggest that classical hallucinogens in the animal model merit further study as a potential approach to the identification of targets for drug discovery and investigation of the neurobiology of addiction.
关于经典致幻剂，尤其是麦角酸二乙酰胺（LSD）用于治疗酒精使用障碍，已有大量临床文献。然而，尚未有关于LSD对动物酒精摄入量影响的已发表研究。本研究采用双瓶选择酒精饮用范式评估了LSD对小鼠的影响。成年雄性C57BL/6J小鼠接触乙醇以形成偏好，然后根据乙醇摄入量分为三组，每组摄入量相等，随后分别腹腔注射生理盐水或25或50μg/kg的LSD，同时提供水和20%的乙醇。利用重复测量的多级模型将LSD处理组与对照组进行比较。在接受50μg/kg LSD处理的小鼠中，乙醇摄入量相对于对照组有所降低（ = 0.0035），乙醇偏好也有所降低（ = 0.0024），在LSD给药后的46天内，乙醇摄入量的组平均降低持续为17.9%。在接受25μg/kg LSD处理的小鼠中，未观察到对乙醇摄入量或偏好有显著影响。LSD处理组的总液体摄入量和运动活动与对照组相比均无显著差异。这些结果表明，动物模型中的经典致幻剂作为识别药物发现靶点和研究成瘾神经生物学的潜在方法值得进一步研究。
