Introduction
Affecting the γ-amino butyric acid (GABA) pathway results in an alteration of inflammatory response in various animal models. However, its mechanism is still unclear. The aim of this study was to determine the effects of muscimol, a GABAA receptor agonist, on lipopolysaccharide-induced mortality and inflammation in mice.
Materials
C57BL6 mice, lipopolysaccharide (derived from Escherichia coli, serotype O55:B5), and muscimol were used in this study.
Methods
Mice endotoxemia was induced by 10 mg/kg lipopolysaccharide intraperitoneally. Muscimol ranging from 0 to 3 mg/kg were given subcutaneously 30 minutes before lipopolysaccharide administration. Serum TNFα, IL-1β, IL-10, and IL-12 were determined using ELISA.
Results
Muscimol significantly increased the survival rate in sub-lethal dose of lipopolysaccharide-treated mice (from 7% to 100%) (P < 0.0001) within 72 hours. Muscimol inhibited serum TNFα, IL-1β, and IL-12 production in a dose-dependent manner. Furthermore, muscimol significantly increased serum IL-10 levels (P < 0.001) in lipopolysaccharide-treated mice.
Conclusion
Muscimol potently increased the survival rate and inhibited inflammatory response in endotoxemic mice.