Abstract：Objective: To observe the effects of oleanolic acid on schizophrenia-like behaviors in mice elicited by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. Methods: Effects of oleanolic acid via oral gavage in MK-801-induced schizophrenia-like response in mice, such as open field test, acoustic startle response test and novel object recognition test were all observed. Results: Singlely administration of oleanolic acid blocked MK-801-induced hyperlocomotion in the open field test. In acoustic startle response test, oleanolic acid did not affect the acoustic startle response or prepulse inhibition (PPI) level. And MK-801-induced PPI deficit was ameliorated by oleanolic acid. In novel object recognition test, attention and recognition memory impairments induced by MK-801 were reversed by oleanolic acid. Additionally, oleanolic acid normalized the MK-801-induced alterations of signaling molecules, including phosphorylation levels of Akt and GSK-3β in frontal cortex. Conclusion: These results suggest that oleanolic acid can be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, and cognitive impairments.
