裸盖菇素通过干扰与酒精相关记忆的再巩固来防止酒精觅药行为的再现。
Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories.
机构信息
School of Pharmacy, Center for Neuroscience, University of Camerino, Camerino, Italy.
出版信息
Psychopharmacology (Berl). 2023 Jul;240(7):1521-1530. doi: 10.1007/s00213-023-06384-w. Epub 2023 Jun 2.
BACKGROUND
For most psychiatric conditions, including alcohol use disorder (AUD), FDA-approved pharmacological treatments are limited and their efficacy is restricted to only certain subgroups of patients. Scientific interest in the potential of psychedelic drugs has dramatically increased because of clinical preliminary evidence of efficacy in treating various psychiatric disorders. One of the most promising compounds belonging to this class of molecules is psilocybin. Here, to elucidate the therapeutic potential and treatment modalities of this drug, we investigated the effect of psilocybin on alcohol drinking and seeking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, a well validated animal model of AUD characterized by excessive drinking and seeking.
METHODS
Using male and female msP rats, we tested the effect of psilocybin on home cage voluntary alcohol consumption. We also tested the effect of the drug on the alcohol deprivation effect (ADE) model of relapse and on cue-induced reinstatement of alcohol seeking after a period of abstinence. Finally, we evaluated if psilocybin may disrupt the reconsolidation process of alcohol-related memory.
RESULTS
Psilocybin did not reduce alcohol consumption, nor it prevented increased alcohol drinking after a period of forced abstinence and cue-induced reinstatement of alcohol-seeking. Noteworthy, in a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated resumption of alcohol seeking.
CONCLUSIONS
Altogether these data suggest that, despite psilocybin does not affect alcohol drinking and relapse, it may be highly effective if used to block the reconsolidation process of alcohol-related memories. This opens to the possibility of using this psychedelic drug in clinical settings in which AUD patients undergo procedures to recall the memory of alcohol and are then treated with psilocybin during the memory reconsolidation phase.
背景
对于大多数精神疾病，包括酒精使用障碍（AUD），FDA 批准的药物治疗方法有限，其疗效仅限于某些特定的患者亚组。由于临床初步证据表明治疗各种精神障碍有效，人们对迷幻药物的潜在应用产生了浓厚的兴趣。属于这一类分子的最有前途的化合物之一是裸盖菇素。在这里，为了阐明这种药物的治疗潜力和治疗方式，我们研究了裸盖菇素对遗传选择的 Marchigian Sardinian 酒精偏好（msP）大鼠的酒精摄入和觅酒行为的影响，这是一种经过充分验证的 AUD 动物模型，其特征是过度饮酒和觅酒。
方法
我们使用雄性和雌性 msP 大鼠，测试了裸盖菇素对其在笼内自愿饮酒的影响。我们还测试了该药物对酒精剥夺效应（ADE）复发模型和在一段禁欲期后，线索诱导的觅酒复吸的影响。最后，我们评估了裸盖菇素是否可能破坏与酒精相关的记忆的再巩固过程。
结果
裸盖菇素既没有减少酒精的摄入量，也没有预防在强制禁欲和线索诱导的觅酒复吸后饮酒量的增加。值得注意的是，在记忆检索-再巩固范式中，裸盖菇素显著抑制了酒精觅酒行为的恢复。
结论
总的来说，这些数据表明，尽管裸盖菇素不会影响酒精的摄入和复发，但如果用于阻断与酒精相关的记忆的再巩固过程，它可能非常有效。这为在临床环境中使用这种迷幻药物提供了可能性，在这些环境中，AUD 患者接受程序来回忆与酒精相关的记忆，然后在记忆再巩固阶段用裸盖菇素进行治疗。
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