关键词: 5-HTP Egr1 Egr2 cfos hTR psilocybin psychedelics

来  源:   DOI:10.3389/fphar.2024.1391412   PDF(Pubmed)

Abstract:
Background: Immediate early genes (IEGs) are rapidly activated and initiate diverse cellular processes including neuroplasticity. We report the effect of psilocybin (PSIL), PSIL-containing psychedelic mushroom extract (PME) and 5-hydroxytryptophan (5-HTP) on expression of the IEGs, cfos, egr1, and egr2 in mouse somatosensory cortex (SSC). Methods: In our initial experiment, male C57Bl/6j mice were injected with PSIL 4.4 mg/kg or 5-HTP 200 mg/kg, alone or immediately preceded by serotonergic receptor modulators. IEG mRNA expression 1 hour later was determined by real time qPCR. In a replication study a group of mice treated with PME was added. Results: In our initial experiment, PSIL but not 5-HTP significantly increased expression of all three IEGs. No correlation was observed between the head twitch response (HTR) induced by PSIL and its effect on the IEGs. The serotonergic receptor modulators did not significantly alter PSIL-induced IEG expression, with the exception of the 5-HT2C antagonist (RS102221), which significantly enhanced PSIL-induced egr2 expression. 5-HTP did not affect IEG expression. In our replication experiment, PSIL and PME upregulated levels of egr1 and cfos while the upregulation of egr2 was not significant. Conclusions: We have shown that PSIL and PME but not 5-HTP (at a dose sufficient to induce HTR), induced a significant increase in cfos and egr1 expression in mouse SSC. Our findings suggest that egr1 and cfos expression may be associated with psychedelic effects.
摘要:
背景:即时早期基因(IEG)被迅速激活并启动包括神经可塑性在内的多种细胞过程。我们报告了psilocybin(PSIL)的作用,含PSIL的迷幻蘑菇提取物(PME)和5-羟色氨酸(5-HTP)对IEGs表达的影响,cfos,小鼠体感皮层(SSC)中的egr1和egr2。方法:在我们最初的实验中,雄性C57Bl/6j小鼠注射PSIL4.4mg/kg或5-HTP200mg/kg,单独或紧接在血清素能受体调节剂之前。通过实时qPCR测定1小时后的IEGmRNA表达。在复制研究中,加入一组用PME处理的小鼠。结果:在我们最初的实验中,PSIL而不是5-HTP显著增加所有三种IEG的表达。PSIL诱导的头部抽搐反应(HTR)与其对IEG的影响之间没有相关性。5-羟色胺能受体调节剂没有显著改变PSIL诱导的IEG表达,除5-HT2C拮抗剂(RS102221)外,显著增强了PSIL诱导的egr2表达。5-HTP不影响IEG表达。在我们的复制实验中,PSIL和PME上调了egr1和cfos的水平,而egr2的上调不显着。结论:我们已经表明PSIL和PME而不是5-HTP(在足以诱导HTR的剂量下),诱导小鼠SSC中cfos和egr1表达的显着增加。我们的发现表明,egr1和cfos的表达可能与迷幻作用有关。
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