Psychedelic 25H-NBOMe attenuates post-sepsis depression in rats

Sepsis-associated encephalopathy, which manifests in severe cognitive and depressive symptoms, is directly linked to neuroinflammation. Our study investigates the efficacy of 25H-NBOMe, a phenethylamine, in alleviating these symptoms, potentially offering an innovative treatment for post-sepsis depr...

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Published in:Neuroscience letters 2024-06, Vol.834, p.137845, Article 137845
Main Authors: Ferri, Barbara G., de Novais, Cintia O., Rojas, Viviana C.T., Estevam, Elisa S., dos Santos, Gabriel J.M, Cardoso, Rayner R., Nogueira, Ester S.C., Oliveira, Pollyanna F., de Barros, Wellington A., de Fátima, Ângelo, Vilela Giusti, Fabiana C., Giusti-Paiva, Alexandre
Format: Article
Language:English
Subjects:
Animal models
Forced swimming test
Long-term sequelae
Neuroinflammation
Phenethylamine
Sepsis-associated encephalopathy
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Summary:Sepsis-associated encephalopathy, which manifests in severe cognitive and depressive symptoms, is directly linked to neuroinflammation. Our study investigates the efficacy of 25H-NBOMe, a phenethylamine, in alleviating these symptoms, potentially offering an innovative treatment for post-sepsis depression. Wistar rats, weighing between 250–300 g, were subjected to cecal ligation and puncture (CLP) surgery to induce sepsis. Depressive-like behaviors were assessed using the forced swim test (FST) on either day 7 or 14 post-surgery, to establish the presence of depressive symptoms. The impact of 25H-NBOMe treatment was then evaluated, focusing on the head-twitch response (HTR), performance in the FST, and GFAP expression in the prefrontal cortex. Treatment with 25H-NBOMe resulted in significant behavioral changes, demonstrated by decreased immobility and increased swimming times in the FST, along with a rise in the HTR. These outcomes indicate a reduction in depressive-like symptoms post-sepsis and the psychoactive effects of the compound. Furthermore, a notable decrease in GFAP expression in the study highlights the compound’s impact on mitigating sepsis-induced astrogliosis. This study demonstrates the effectiveness of 25H-NBOMe, a psychedelic in the phenethylamine class, in treating post-sepsis depression and reducing astrogliosis. However, the psychedelic nature of 25H-NBOMe calls for further investigation into similar compounds with less psychoactive impact, crucial for advancing treatment options for neuropsychiatric symptoms following sepsis.
ISSN:0304-3940
1872-7972
1872-7972
DOI:10.1016/j.neulet.2024.137845