Methylene blue exerts rapid neuroprotective effects on lipopolysaccharide-induced behavioral deficits in mice

•LPS injection induced depression-like behaviours and memory impairments.•Methylene blue treatment blocked LPS-induced depression-like behaviours.•Methylene blue treatment reversed LPS-induced memory impairments.•Peripheral HO1 level may be involved in fast-acting effects of methylene blue. Depression is a recurrent neuropsychiatric disorder accompanied with other behavioral deficits, including memory impairment. A few studies have shown that methylene blue (MB) could promote cortical neurogenesis and exert neuroprotective effects on various brain diseases, including bipolar disorder. However, the potential antidepressant effects of MB have not been fully investigated. The present study was designed to investigate the effects of MB pretreatment on behavioral deficits and the underlying mechanisms in a lipopolysaccharide (LPS)-induced depression mouse model. Mice were given saline (5 mL/kg) or MB (5, 20 mg/kg) intraperitoneally (i.p.) 30 min prior to lipopolysaccharide (LPS, 800 μg/kg, i.p.) or the following behavioral tests. Thereafter, serum heme oxygenase 1(HO1) were determined by ELISA. The results showed that LPS significantly induced body weight loss and behavioral deficits that included increased floating time in the forced swimming test, increased immobility time in the tail suspension test, decreased sucrose preference in the sucrose preference test, and memory impairment in the novel object recognition (all p