Administration of moclobemide facilitates fear extinction and attenuates anxiety‐like behaviors by regulating synaptic‐associated proteins in a rat model of post‐traumatic stress disorder

Post‐traumatic stress disorder (PTSD) is a long‐lasting mental disorder and accompanied by worse fear extinction. Enhanced fear memory or poor fear extinction are typical features of PTSD. Dysfunction of the serotonergic neurotransmitter system is involved in numerous mental and behavioral disorders. Monoamine oxidase A (MAOA) is important in the metabolism of serotonin and play an important role in behavious. The aim of this study was to explore the change of MAOA and effect of MAOA on fear memory in PTSD. We used single prolonged stress (SPS) to create animal model of PTSD. A startle/fear box and elevated plus maze were used to observe fear memory and anxiety level, respectively. We examined the expression of MAOA and synaptic marker protein, as well as the immunological activity of MAOA in the infralimbic cortex (IL) area, which is a critical brain region involved in emotions, especially fear regulation. We found increased anxiety‐like behavior, dysfunction in fear extinction, and increased MAOA in SPS rats. After treatment with moclobemide (a selective inhibitor of MAOA), SPS rats showed significantly improved fear memory and decreased anxiety‐like behavior, which indicated that moclobemide could reverse fear extinction deficit and attenuate abnormally increased levels of anxiety caused by SPS in short term. On the contrary, decreased PSD‐95 and SYN1 expression in the IL region were also reversed by moclobemide. These results suggest that increased MAOA play a negative role in fear extinction and levels of anxiety in PTSD, which may be involved in change in PSD‐95 and SYN1. This graph showed the experimental process of the present study. Single prolonged stress (SPS) was used to create animal model of PTSD. Rats after SPS stimuli exhibited increased levels of anxiety and fear memory, increased MAOA expression in the infralimbic cortex (IL) area, but decreased plasticity‐associated marker proteins expression. After early intervention with moclobemide (a selective inhibitor of MAOA), SPS rats showed significantly improved fear memory and decreased anxiety‐like behavior, which was accompanied by increased plasticity‐associated marker proteins expression.