Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour

IF 4.6 2区 医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2024-11-02 DOI:10.1016/j.neuropharm.2024.110202
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Abstract

Psilocybin is a serotonergic psychedelic compound which shows promise for treating compulsive behaviours. This is particularly pertinent as compulsive disorders require research into new pharmacological treatment options as the current frontline treatments such as selective serotonin reuptake inhibitors, require chronic administration, have significant side effects, and leave almost half of the clinical population refractory to treatment.
In this study, we investigated psilocybin administration in male and female SAPAP3 knockout (KO) mice, a well-validated mouse model of obsessive compulsive and related disorders. We assessed the effects of acute psilocybin (1 mg/kg, intraperitoneal) administration on head twitch and locomotor behaviour as well as anxiety- and compulsive-like behaviours at multiple time-points (1, 3 and 8 days post-injection).
While psilocybin did not have any effect on anxiety-like behaviours, we revealed that acute psilocybin administration led to enduring reductions in compulsive behaviour in male SAPAP3 KO mice and reduced grooming behaviour in female wild-type (WT) and SAPAP3 KO mice. We also found that psilocybin increased locomotion in WT littermates but not in SAPAP3 KO mice, suggesting in vivo serotonergic dysfunctions in KO animals. On the other hand, the typical head-twitch response following acute psilocybin (confirming its hallucinogenic-like effect at this dose) was observed in both genotypes.
Our novel findings suggest that acute psilocybin may have potential to reduce compulsive-like behaviours (up to 1 week after a single injection). Our study can inform future research directions as well as supporting the utility of psilocybin as a novel treatment option for compulsive disorders.
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迷幻药可减少 SAPAP3 基因敲除小鼠强迫行为模型中的梳理行为。
迷幻药是一种血清素能迷幻化合物,有望治疗强迫行为。这一点尤为重要,因为强迫症需要研究新的药物治疗方案,因为目前的一线治疗药物(如选择性 5-羟色胺再摄取抑制剂)需要长期用药,副作用大,而且几乎有一半的临床人群对治疗不耐受。在这项研究中,我们研究了在雄性和雌性 SAPAP3 基因敲除(KO)小鼠中服用迷幻药的情况。我们在多个时间点(注射后 1 天、3 天和 8 天)评估了急性服用迷幻药(1 毫克/千克,腹腔注射)对头部抽搐和运动行为以及焦虑和强迫行为的影响。虽然迷幻药对焦虑样行为没有任何影响,但我们发现,急性迷幻药注射会导致雄性 SAPAP3 KO 小鼠强迫行为的持续减少,以及雌性野生型(WT)和 SAPAP3 KO 小鼠梳理行为的减少。我们还发现,迷幻药能增加WT同窝小鼠的运动能力,但不能增加SAPAP3 KO小鼠的运动能力,这表明KO动物体内存在血清素能障碍。另一方面,两种基因型的小鼠在服用急性迷幻药后都出现了典型的头部抽搐反应(证实了该剂量下的致幻效应)。我们的新发现表明,急性西洛赛宾可能具有减少类似强迫症行为的潜力(单次注射后可持续一周)。我们的研究可以为未来的研究方向提供信息,并支持将迷幻药作为治疗强迫症的一种新方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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