Peripheral LPS challenge affects monoamine neurotransmitter levels in the nucleus accumbens

Pro-inflammatory cytokines are produced in response to peripheral infection and could directly and indirectly influence the brain. Evidence points to a role of neuroimmune mechanisms in major depressive disorder mediated by pro-inflammatory cytokines. First of all do depressed patients show increased serum levels of proinflammatory cytokines. Furthermore is depression a side-effect of IFN-alpha used in the treatment of patients with hepatitis C. Lipopolysacharide (LPS) is a constituent of the outer membrane of Gram-negative bacteria and induces depression-like behavior in several animal models. Binding of LPS to toll-like receptor 4 (TLR4) induces the production of pro-inflammatory cytokines. It is well known that depressed patients show alterations in monoamine neurotransmission. Pro-inflammatory cytokines, upregulated by LPS, might induce changes in monoamine neurotransmission, which results in depression. The aim of the present study was to measure extracellular monoamine concentrations in the nucleus accumbens (NAc) after activation of the TLR4 signaling pathway by a single i.p. injection of LPS in C57BL/6 mice. LPS treatment resulted in increased levels of the breakdown products of serotonin and dopamine (5-HIAA, DOPAC and HVA). These results demonstrate that peripheral administration of LPS leads to alterations in brain monoamine neurotransmission. This suggests that TLR4 signaling and pro-inflammatory cytokines play a role in the communication between the immune and central nervous system. More research is needed to investigate whether cytokineinduced depression can be treated by drugs and/or nutrition.