Low-dose DOI pretreatment reduces inflammation and sickness-like behavior after immune challenge in male mice

A small study in male mice found that a low dose of DOI administered 24 hours before an immune challenge reduced hippocampal inflammation and sickness-like behavioral changes. The challenge used lipopolysaccharide, a bacterial molecule that triggered peaks in the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor alpha. DOI pretreatment lowered both markers in unmodified mice, prevented reduced movement and passive behavior in swimming tests, and lessened weight loss. Experiments in mice lacking the serotonin 5-HT2A receptor showed that suppression of interleukin-6 depended on this receptor, while the reduction in tumor necrosis factor alpha appeared to involve additional pathways. The higher DOI dose was ineffective, possibly because excessive receptor activation can reduce signaling. The findings suggest a potential preventative immune-modulating effect, but they do not establish therapeutic benefits in humans. Limitations include the acute model, whole-tissue measurements, possible effects outside the brain, lifelong receptor deletion in modified mice, and the use of male animals only.