Figure 5.

A schematic diagram of how LPS may induce depression-like behaviors and how the α7 nAChR and NMDA receptor antagonists together exert antidepressant-like effects in LPS-mediated inflammatory model of MDD. (1) PNU120596 positively modulates the α7 nAChR via the allosteric binding site. This activation prevents LPS-induced increase in HAAO expression and QUIN formation in the hippocampus (HPC) and prefrontal cortex (PFC). (2) Inhibition of the NMDA receptor-mediated glutamatergic neurotransmission, induced by QUIN, by memantine reduced LPS-induced depression-like behavior. (3) Memantine enhances the antidepressant-like effects of PNU120596, suggesting the interaction between α7 nAChR and NMDA receptor mediating depression-like behavior in mice. →: stimulation; ─┤: inhibition.