Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 2100, Denmark.
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 2100, Denmark.
Behav Brain Res. 2021 Mar 5;401:113093. doi: 10.1016/j.bbr.2020.113093. Epub 2020 Dec 28.
Psychedelic drugs acting as 5-hydroxyptryptamine 2A receptor (5-HTR) agonists have shown promise as viable treatments of psychiatric disorders, including obsessive-compulsive disorder. The marble burying test is a test of compulsive-like behavior in mice, and psychedelics acting as 5-HTR agonists can reduce digging in this test. We assessed the 5-HTR contribution to the mechanisms of two 5-HT agonists on digging behavior in female NMRI mice, using citalopram as a reference compound. While the 5-HTR antagonist M100907 blocked the effect of DOI and the 5-HTR antagonist SB242084 blocked the effect of citalopram, neither antagonist blocked the effect of psilocybin. This study confirms 5-HTR agonism as a mechanism for reduced compulsive-like digging in the MB test and suggests that 5-HT and 5-HTRs can work in parallel on this type of behavior. Our results with psilocybin suggest that a 5-HTR-independent mechanism also contributes to the effect of psilocybin on repetitive digging behavior.
致幻剂作为 5-羟色胺 2A 受体（5-HTR）激动剂，已显示出作为治疗精神疾病（包括强迫症）的可行方法的潜力。大理石掩埋试验是一种测试小鼠强迫行为的试验，作为 5-HTR 激动剂的致幻剂可以减少这种试验中的挖掘行为。我们使用西酞普兰作为参考化合物，评估了两种 5-HT 激动剂对 NMRI 雌性小鼠挖掘行为的 5-HTR 贡献机制。虽然 5-HTR 拮抗剂 M100907 阻断了 DOI 的作用，5-HTR 拮抗剂 SB242084 阻断了西酞普兰的作用，但两种拮抗剂都没有阻断裸盖菇素的作用。这项研究证实了 5-HTR 激动剂是减少 MB 试验中强迫性挖掘的一种机制，并表明 5-HT 和 5-HTR 可以在这种行为上并行工作。我们对裸盖菇素的研究结果表明，5-HTR 不依赖的机制也有助于裸盖菇素对重复性挖掘行为的影响。
