Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2,3-dioxygenase-dependent depression-like behaviors

• Published in: Journal of neuroinflammation Vol. 10; no. 1; p. 87
• Main Authors: Lawson, Marcus A, Parrott, Jennifer M, McCusker, Robert H, Dantzer, Robert, Kelley, Keith W, O'Connor, Jason C
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.07.2013; BioMed Central
• Subjects: Animals; Antidepressive Agents - therapeutic use; Behavior; Brain - drug effects; Brain - metabolism; Brain research; Depression - chemically induced; Depression - drug therapy; Depression - genetics; Depression - pathology; Depression, Mental; Disease; Disease Models, Animal; Dosage and administration; Enzymes; Exploratory Behavior - drug effects; Food Preferences - drug effects; Indoleamine-Pyrrole 2,3,-Dioxygenase - deficiency; Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics; Inflammation; Injections, Intraventricular; Lipopolysaccharides; Lipopolysaccharides - administration & dosage; Male; Medical research; Metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mitogens; Neurosciences; Physiological aspects; Rodents; Science; Studies; Sucrose - administration & dosage; Time Factors; Tryptophan; Tryptophan - analogs & derivatives; Tryptophan - blood; Tryptophan - therapeutic use; Up-Regulation - drug effects; United States
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/1742-2094-10-87

Activation of the tryptophan degrading enzyme indoleamine-2,3-dioxygenase 1 (IDO1) is associated with the development of behavioral signs of depression. Systemic immune challenge induces IDO1 in both the periphery and the brain, leading to increased circulating and brain concentrations of kynurenines. However, whether IDO1 activity within the brain is necessary for the manifestation of depression-like behavior of mice following a central immune challenge remains to be elucidated. We investigated the role of brain IDO1 in mediating depression-like behavior of mice in response to intracerebroventricular injection of saline or lipopolysaccharide (LPS, 10 ng). LPS increased the duration of immobility in the tail suspension test and decreased preference for a sucrose solution. These effects were associated with an activation of central but not peripheral IDO1, as LPS increased brain kynurenine but had no effect on plasma concentrations of kynurenine. Interestingly, genetic deletion or pharmacological inhibition of IDO1, using 1-methyl-tryptophan, abrogated the reduction in sucrose preference induced by intracerebroventricular LPS. 1-Methyl-tryptophan also blocked the LPS-induced increase in duration of immobility during the tail suspension test. These data indicate that activation of brain IDO1 is sufficient to induce depression-like behaviors of mice in response to central LPS.