Effect of ketamine combined with DHA on lipopolysaccharide-induced depression-like behavior in rats.

Ketamine combined with docosahexaenoic acid (DHA), an unsaturated fatty acid, reversed depression-like behaviors in rats exposed to lipopolysaccharide, an inflammatory trigger. The combination reduced immobility time in forced swimming and tail suspension tests and increased sucrose preference more effectively than either agent alone. It also reversed nerve damage, reduced inflammatory cytokines IL-1, IL-6, and TNF-α in the hippocampus and PC12 cells, increased brain-derived neurotrophic factor (BDNF), inhibited PP65 nuclear translocation, and suppressed NF-κB expression while increasing P-CREB and BDNF. The findings suggest that combining ketamine with DHA may offer a more effective treatment for inflammation-driven depression by inhibiting inflammatory pathways.

Study at a glance

Abstract

Depression has become a common mental illness, and studies have shown that neuroinflammation is associated with depression. Ketamine is a rapid antidepressant. In order to obtain better antidepressant effects, it is necessary to explore the efficacy of combination therapy with ketamine and other antidepressants. DHA is an unsaturated fatty acid with excellent application prospects due to its safety and antidepressant effects. This study was designed to investigate the effect of ketamine combined with DHA on lipopolysaccharide-induced depression-like behavior. In behavioral experiments, lipopolysaccharide prolongs the immobility time of the forced swimming and tail suspension tests in rats and reduces the sucrose preference. The combination of ketamine and DHA can reverse these changes and work better than the single application. Nissl staining showed that ketamine combined with DHA can reverse the nerve damage caused by lipopolysaccharide. Cell morphology observation the combination of ketamine and DHA group was more complete than that of LPS group. The combination of ketamine and DHA significantly decreased the levels of IL-1, IL-6 and TNF-ɑin hippocampus and PC12 cells and increased the content of BDNF. Immunofluorescence results showed that ketamine combined with DHA can effectively inhibit PP65 nuclear translocation. Western blot results showed that ketamine combined with DHA can effectively inhibit the expression of NF-KB in hippocampus and PC12 cells, and increase the expression of P-CREB and BDNF. In summary, the combination of ketamine with DHA may be a more effective treatment for depression caused by inflammation and is mediated by inhibition of the inflammatory pathway.