5-羟色胺能
灵霉素
抗焦虑药
药理学
抗抑郁药
尾部悬挂试验
行为绝望测验
致幻剂
血清素
心理学
麦角酸二乙酰胺
内科学
焦虑
医学
受体
精神科
作者
Rika Takaba,Daisuke Ibi,Keisuke Yoshida,Eriko Hosomi,Ryota Kawase,Hiroko Kitagawa,Hiroaki Goto,Motonobu Achiwa,Kazuki Mizutani,Kyosuke Maede,Javier González-Maeso,Shinji Kitagaki,Masayuki Hiramatsu
出处
期刊:Research Square - Research Square
日期:2023-07-07
标识
DOI:10.21203/rs.3.rs-3138705/v1
摘要
Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT 2A 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. 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 24 h post-treatment. 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 an anxiolytic effects.
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