Objective To explore the molecular mechanism of enhancing the effect of risperidone on the cognitive function of schizophrenic mice by fluoxetine. Methods Schizophrenic mice were injected with M K-801 and drugs( fluoxetine and / or risperidone) were adm inistrated orally 30 min before the injection of M K-801.Mice of the control group adm inistrated the same dose of norm al saline. The cognitive function, distance of activity, and stereotyped behavior of mice were observed. The expressions of key param eters of MEK / ERK pathway in hippocam pus were detected by Western blotting or real-time qPCR. The participation of MEK / ERK pathway in isolated hippocam palneuron injuries induced by M K-801 mediation was also analyzed. Results The mice of M K-801 group showed prolonged activity distance, increased stereotyped behavior scores, and cognitive im pairm ent. Expressions of pMEK/MEK, pERK/ERK1 /2, MMP2 /9, and TIMP1 /2 of the MK-801 group increased. The aforem entioned proteins of drug adm inistration groups decreased dram atically. For schizophrenic m ice, fluoxetine enhanced effects of risperidone in norm alizing abnorm al behaviors, affecting cognitive function, and unusual protein expressions( P < 0. 05). Results of in vitro experim ents were sim ilar to those of in vivo experim ents. Conclusion Fluoxetine enhances the anti-schizophrenic effect of risperidone by norm alizing the activated MEK / ERK signaling pathway.
