Prostaglandins mediate depressive-like behaviour induced by endotoxin in mice

Abstract

Sickness behaviour appears to be the expression of a central motivational state that reorganises the organism's priorities to cope with infectious pathogens. To evaluate the possible participation of prostaglandins in lipopolysaccharide-induced sickness behaviours, mice were submitted to the tail suspension test (TST), forced swim test (FST), open field test and dark–light box test. Lipopolysaccharide (LPS, 100 μg/kg; i.p.) administration increased the time spent immobile in the TST, increased the time spent floating in the FST, and depressed locomotor activity in the open field. Indeed, treatment with LPS decreased the total number of transitions made between the dark and light compartments of the apparatus. Pretreatment with indomethacin (10 mg/kg; i.p.) or nimesulide (5 mg/kg) blocked behavioural changes induced by LPS in the FTS, TST, open field and light–dark box test. This effect was similar to pretreatment with dexamethasone (1 mg/kg), which is a steroidal drug that inhibits immune and inflammatory responses, including cytokine production. These findings confirm previous observations that have reported LPS-induced sickness behaviours. In addition, they provide evidence that the synthesis of prostaglandins is necessary for changes in depressive-like and exploratory behaviours in mice, which is supported by the fact that COX inhibitors also attenuate LPS-induced behavioural changes.