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Neuropharmacology. 2014 Nov;86:49-56. doi: 10.1016/j.neuropharm.2014.06.025. Epub 2014 Jul 2.

Oleanolic acid attenuates MK-801-induced schizophrenia-like behaviors in mice.

Author information

1
Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, Republic of Korea.
2
Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
3
Department of Pharmacy and Uimyong Research Institute for Neuroscience, Sahmyook University, Seoul, Republic of Korea.
4
Department of Neuroscience, School of Medicine and Neuroscience Research Center, Institute SMART-IABS, Konkuk University, Seoul, Republic of Korea.
5
Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, Republic of Korea; Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.

Abstract

Schizophrenia is a severe neuropsychiatric disorder that is characterized by core psychiatric symptoms, including positive, negative, and cognitive symptoms. Current treatments for schizophrenia have an effect on positive symptoms but have a limited efficacy on negative or cognitive symptoms. Oleanolic acid is a plant-derived pentacyclic terpenoid that is known to exhibit anti-oxidative and anti-inflammatory activities. Here, we investigated the effects of oleanolic acid on schizophrenia-like behaviors in mice elicited by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. A single administration of oleanolic acid blocked MK-801-induced hyperlocomotion in the open field test. In the acoustic startle response test, oleanolic acid itself did not have any effects on the acoustic startle response or prepulse inhibition (PPI) level, whereas the MK-801-induced PPI deficit was ameliorated by oleanolic acid. In the novel object recognition test, the attention and recognition memory impairments induced by MK-801 were reversed by a single administration of oleanolic acid. Additionally, oleanolic acid normalized the MK-801-induced alterations of signaling molecules including phosphorylation levels of Akt and GSK-3β in the frontal cortex. These results suggest that oleanolic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, and cognitive impairments.

KEYWORDS:

MK-801; Memory impairment; Oleanolic acid; Prepulse inhibition; Schizophrenia

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