Repeated Administration of LPS Exaggerates Amphetamine-induced Locomotor Response and Causes Learning Deficits in Mice

Immune activation contributes to the pathophysiology of psychiatric disorders. Administration of a single dose of lipopolysaccharides (LPS) has been shown to induce depressive- and anxiety-like behaviors in rodents through activation of the kynurenine pathway, increasing levels of the N-methyl-d-aspartate (NMDA) receptor agonist quinolinic acid. Conversely, repeated administration of LPS produces increased levels of the NMDA receptor antagonist kynurenic acid. Here we show that repeated LPS administration increases sensitivity to D-amphetamine and produces cognitive deficits and anxiety-like behavior. Together, our behavioral data suggests that repeated LPS administration may be useful to study the contribution of inflammation to psychiatric disorders such as schizophrenia.