{Reference Type}: Journal Article {Title}: Psychedelic 25H-NBOMe attenuates post-sepsis depression in rats. {Author}: Ferri BG;de Novais CO;Rojas VCT;Estevam ES;Dos Santos GJM;Cardoso RR;Nogueira ESC;Oliveira PF;de Barros WA;de Fátima Â;Vilela Giusti FC;Giusti-Paiva A; {Journal}: Neurosci Lett {Volume}: 834 {Issue}: 0 {Year}: 2024 Jun 21 {Factor}: 3.197 {DOI}: 10.1016/j.neulet.2024.137845 {Abstract}: 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.