Prostaglandins mediate depressive-like behaviour induced by endotoxin in mice

▶ COX inhibitors blocked behavioural changes induced by endotoxin in the forced swimming test, tail suspension test, open field and light-dark box test. ▶ Prostaglandins are necessary for the development of endotoxin-induced sickness behaviour, independently of cytokines. Sickness behaviour appears...

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Published in:	Behavioural brain research Vol. 215; no. 1; pp. 146 - 151
Main Authors:	de Paiva, Viviane N., Lima, Samuel N.P., Fernandes, Mateus M., Soncini, Roseli, Andrade, Carina A.F., Giusti-Paiva, Alexandre
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier B.V 20-12-2010 Elsevier
Subjects:	Adult and adolescent clinical studies Analysis of Variance Animals Behavior, Animal - drug effects Behavioral psychophysiology Biological and medical sciences Cyclooxygenase Inhibitors - pharmacology Cytokines Depression Depression - chemically induced Depression - metabolism Dexamethasone - pharmacology Endotoxin Exploratory Behavior - drug effects Feeding Behavior - drug effects Fundamental and applied biological sciences. Psychology Glucocorticoids - pharmacology Hindlimb Suspension Illness Behavior Indomethacin - pharmacology Lipopolysaccharides - pharmacology Medical sciences Mice Mood disorders Motor Activity - drug effects Prostaglandins - metabolism Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Psychopathology. Psychiatry Sepsis Sickness behaviour Stress Stress, Physiological - drug effects Sulfonamides - pharmacology Tail Sepsis Endotoxin Sickness behaviour Stress Mood disorder Prostaglandin Arachidonic acid derivatives Rodentia Depression Infection Sepsis syndrome Toxin Vertebrata Mammalia Mouse Eicosanoid Animal Behavior
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Summary:	▶ COX inhibitors blocked behavioural changes induced by endotoxin in the forced swimming test, tail suspension test, open field and light-dark box test. ▶ Prostaglandins are necessary for the development of endotoxin-induced sickness behaviour, independently of cytokines. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0166-4328 1872-7549
DOI:	10.1016/j.bbr.2010.07.015