A study published in Mol Psychiatry (2009) investigates the role of indoleamine 2,3-dioxygenase (IDO) in lipopolysaccharide (LPS)-induced depressive-like behavior in mice. LPS, a component of bacterial cell walls, activates IDO, leading to a depressive-like syndrome characterized by increased immobility in the forced swim and tail suspension tests. This effect is blocked by IDO inhibitors such as minocycline and 1-methyltryptophan (1-MT), which also normalize the kynurenine/tryptophan ratio in plasma and brain without affecting serotonin turnover. Administration of kynurenine, a product of IDO activity, induces depressive-like behavior in naive mice, suggesting IDO is a critical mediator of inflammation-induced depression. The study shows that IDO activation leads to the catabolism of tryptophan along the kynurenine pathway, generating neuroactive metabolites that contribute to depressive-like behaviors. These findings highlight IDO as a key molecular mediator in the link between inflammation and depression, with potential therapeutic implications for inflammation-associated depressive disorders.A study published in Mol Psychiatry (2009) investigates the role of indoleamine 2,3-dioxygenase (IDO) in lipopolysaccharide (LPS)-induced depressive-like behavior in mice. LPS, a component of bacterial cell walls, activates IDO, leading to a depressive-like syndrome characterized by increased immobility in the forced swim and tail suspension tests. This effect is blocked by IDO inhibitors such as minocycline and 1-methyltryptophan (1-MT), which also normalize the kynurenine/tryptophan ratio in plasma and brain without affecting serotonin turnover. Administration of kynurenine, a product of IDO activity, induces depressive-like behavior in naive mice, suggesting IDO is a critical mediator of inflammation-induced depression. The study shows that IDO activation leads to the catabolism of tryptophan along the kynurenine pathway, generating neuroactive metabolites that contribute to depressive-like behaviors. These findings highlight IDO as a key molecular mediator in the link between inflammation and depression, with potential therapeutic implications for inflammation-associated depressive disorders.