Abstract：
Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear. In this study, we ethopharmacologically analyzed the role of 5-HT2A in the occurrence of anxiolytic- and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice 24 h post-treatment. Mice with acute intraperitoneal psychedelic treatment exhibited significantly shorter immobility times in the forced swimming test (FST) and tail-suspension test (TST) than vehicle-treated control mice. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the novelty-suppressed feeding test (NSFT), the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not diminish this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. These results suggest that 5-HT2A contributes to the antidepressant effects of serotonergic psychedelics rather than anxiolytic effects.
摘要：
血清素能迷幻药如psilocybin,麦角酰二乙胺，和DOI通过5-羟色胺5-HT2A受体（5-HT2A）激活发挥幻觉作用。最近的研究表明，5-羟色胺能迷幻药具有治疗神经精神疾病的潜力，包括重度抑郁和焦虑相关疾病。然而,5-HT2A是否参与介导这些药物的治疗效果尚不清楚.在这项研究中,我们从药物药理学上分析了5-HT2A在5-羟色胺能迷幻药如psilocin的抗焦虑和抗抑郁样作用中的作用，psilocybin的活性代谢产物，DOI,和TCB-2在小鼠治疗后24小时。急性腹膜内迷幻剂治疗的小鼠在强迫游泳试验（FST）和尾悬试验（TST）中表现出比媒介物治疗的对照小鼠明显更短的不动时间。这些影响通过用volinanserin预处理消除，5-HT2A拮抗剂。令人惊讶的是,对急性psilocin治疗的FST不动时间减少持续至少3周.在新颖性抑制喂养测试(NSFT)中，要馈送的延迟，焦虑样行为的指标，因急性服用psilocin而减少；然而，用volinanserin预处理并没有减少这种作用。相比之下,DOI和TCB-2不影响小鼠的NSFT表现。此外，psilocin,DOI,和TCB-2治疗不影响自发运动活动或头部抽搐反应，啮齿动物的类似幻觉的行为。这些结果表明，5-HT2A有助于5-羟色胺能迷幻药的抗抑郁作用，而不是抗焦虑作用。
