Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Prague, Czech Republic; Psychedelics Research Centre, National Institute of Mental Health, Klecany, Czech Republic.
Neuroscience. 2024 Nov 1;559:156-165. doi: 10.1016/j.neuroscience.2024.09.006. Epub 2024 Sep 3.
There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects. Few preclinical studies have examined a role for psilocybin in addiction models. The goal of the current study was to determine whether psilocybin would enhance extinction following cocaine self-administration in male and female mice and rats and thus result in an attenuation of cue-induced drug-seeking. In experiments in mice, 16 female and 19 male mice underwent 8d of cocaine self-administration (0.5 mg/kg/infusion) and extinction training. Immediately following extinction trials, mice were injected with vehicle or 1.0 mg/kg psilocybin. Following the conclusion of extinction training, mice were tested for cue-induced reinstatement. In experiments in rats, 24 female and 23 male rats underwent 15d of cocaine self-administration (0.8 mg/kg/infusion) and extinction training. Immediately following extinction trials, rats were injected with vehicle, 1.0 mg/kg psilocybin, or 2.5 mg/kg psilocybin. Following the conclusion of extinction training, rats were tested for cue-induced reinstatement. Psilocybin administered following extinction trials had no effect, as both female and male mice and rats demonstrated significant cue-induced reinstatement. These data suggest that psilocybin is ineffective at altering cocaine-seeking behavior in the paradigm and doses used in the current study. It remains to be seen whether treatment with psilocybin under different conditions may be useful in the long-standing goal of finding pharmacotherapies to treat CUD.
目前，可卡因使用障碍还没有药物治疗方法。最近，人们对迷幻药（如裸盖菇素）治疗精神疾病的潜力产生了极大的兴趣。人体研究表明，单次服用裸盖菇素可以产生持久的效果。很少有临床前研究探讨过裸盖菇素在成瘾模型中的作用。目前的研究目标是确定裸盖菇素是否会增强雄性和雌性小鼠和大鼠可卡因自我给药后的消退，从而减少线索诱导的觅药行为。在小鼠实验中，16 只雌性和 19 只雄性小鼠接受了 8 天的可卡因自我给药（0.5mg/kg/剂量）和消退训练。在消退试验后，立即给小鼠注射载体或 1.0mg/kg 裸盖菇素。在消退训练结束后，对小鼠进行线索诱导复吸测试。在大鼠实验中，24 只雌性和 23 只雄性大鼠接受了 15 天的可卡因自我给药（0.8mg/kg/剂量）和消退训练。在消退试验后，立即给大鼠注射载体、1.0mg/kg 裸盖菇素或 2.5mg/kg 裸盖菇素。在消退训练结束后，对大鼠进行线索诱导复吸测试。在消退试验后给予裸盖菇素没有效果，因为雌性和雄性小鼠和大鼠都表现出明显的线索诱导复吸。这些数据表明，在当前研究中使用的范式和剂量下，裸盖菇素不能改变可卡因的觅药行为。在不同条件下使用裸盖菇素治疗是否能长期实现寻找可卡因使用障碍的药物治疗方法，还有待观察。
