128. Subpyrogenic inflammation exacerbates behaviour in chronic stress models of depression

• Published in: Brain, behavior, and immunity Vol. 26; pp. S35 - S36
• Main Authors: Couch, Y, Costas-Nunes, J.P, Strekalova, T, Steinbusch, H.W, Anthony, D.C
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-09-2012
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2012.07.152

Patients suffering from major depression (MD) have been shown to have higher levels of circulating cytokines, and patients undergoing cytokine therapy frequently develop MD. The current hypothesis underlying how this might affect MD development states that these cytokines affect the expression of indoleamine-2,3-monooxygenase (IDO). With this in mind we used a robust and validated model of depression in mice – chronic mild stress (CMS). In order to determine the impact of peripheral inflammation on mood under conditions of stress, we also challenged mice which had undergone CMS with the bacterial endotoxin lipopolysaccharide (LPS). Animals which underwent CMS showed increased immobility in the forced swim test and decreased preference for a sucrose solution. LPS alone did not induce any significant behavioural phenotype. However, when combined with CMS, LPS significantly exacerbated the behavioural responses measured. CNS expression of the 5-HT transporter (SERT) and 5-HT 2 A receptor mRNA, as well as the mRNA for a number of proinflammatory cytokines was also significantly different between groups receiving CMS, CMS and LPS, and LPS alone. These data clearly indicate that a number of molecular changes occur in the serotonergic system, and these changes are exacerbated by a concomitant inflammatory challenge. This work highlights the relationship that exists between the innate immune system and chronic stress.