Poly I:C-induced activation of the immune response is accompanied by depression and anxiety-like behaviours, kynurenine pathway activation and reduced BDNF expression

Abstract

In this study we characterised the ability of the viral mimetic poly I:C to induce a neuroinflammatory response and induce symptoms of depression and anxiety in rats. Furthermore, the ability of poly I:C to deplete central tryptophan and serotonin via induction of indolamine 2,3 dioxygenase (IDO), and also the ability of poly I:C to impact upon expression of the neurotrophin BDNF and its receptor TrkB were examined as potential mechanisms to link inflammation to depression. Poly I:C induced a neuroinflammatory response characterised by increased expression of IL-1β, IL-6, TNF-α and CD11b in frontal cortex and hippocampus. In the first 24h following poly I:C administration rats displayed sickness behaviour characterised by reduced locomotor activity and weight gain. Anhedonia measured using the saccharin preference test was used as an indicator of depressive behaviour, and poly I:C induced depressive behaviour that persisted for up to 72h following administration. Anxiety was measured using the open field test and anxious behaviour was observed 24h following poly I:C, a time-point when sickness behaviour had resolved. These behavioural changes were accompanied by decreased expression of BDNF and TrkB in hippocampus and frontal cortex. In addition, poly I:C increased central IDO expression and increased concentrations of tryptophan, and its metabolite kynurenine. However this activation of the kynurenine pathway did not result in reduced central serotonin concentrations. These findings suggest that depressive and anxiety-like behaviours elicited by poly I:C are associated with a reduction in BDNF signalling, and activation of the kynurenine pathway, but not a reduction in serotonin.