Mountain-Cultivated Ginseng Attenuates Phencyclidine-Induced Abnormal Behaviors in Mice by Positive Modulation of Glutathione in the Prefrontal Cortex of Mice.
Escalating evidence indicates that ginseng treatment protects against psychotoxic behaviors and memory impairment. Although the underlying mechanism of schizophrenia remains elusive, recent investigations proposed that downregulation of glutathione (GSH) can be involved in the pathogenesis of this disorder. Since little is known about the effects of ginseng in a schizophrenia-like animal model, we selected mountain-cultivated ginseng (MG) from a variety of ginseng extracts to investigate the effect of ginseng on the psychosis induced by phencyclidine (PCP) in mice. PCP (10 mg/kg/day, s.c.) was administered for 14 consecutive days. Novel object recognition, forced swimming, and social interaction tests were performed during the withdrawal period of 7 days. In addition, behavioral sensitization to an acute challenge of PCP was evaluated. The parameters of the GSH-dependent system in the prefrontal cortex (PFC) were examined. MG (200 mg/kg, i.p./day) or antipsychotic clozapine (10 mg/kg, p.o./day) was administered for seven consecutive days after the final PCP treatment. PCP significantly produced abnormal behaviors, followed by increases in Nrf2 nuclear translocation, its DNA binding activity, and glutamate-cysteine ligase (GCL) mRNA expression in the PFC. PCP treatment significantly decreased GSH/glutathione disulfide (GSSG) ratio and glutathione peroxidase (GPx) activity. MG significantly attenuated abnormal behaviors and the decreases in GSH/GSSG ratio and GPx activity induced by PCP. MG attenuated the increases in Nrf2 activity and GCL expression caused by PCP. The protective potentials of MG were comparable to those of clozapine. MG ameliorates PCP-induced schizophrenia-like psychosis in mice through the positive modulation of the glutathione system.
1 Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University , Chunchon, Republic of Korea .
The-Vinh
TV
Tran
1 Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University , Chunchon, Republic of Korea .
Eun-Joo
EJ
Shin
2 Department of Oriental Medical Food & Nutrition, Semyung University , Jecheon, Republic of Korea .
Sung Kwon
SK
Ko
1 Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University , Chunchon, Republic of Korea .
Yunsung
Y
Nam
3 Department of Anatomy, Chung-Ang University , Seoul, Republic of Korea .
Yoon Hee
YH
Chung
4 Pharmacology, College of Medicine, Chung-Ang University , Seoul, Republic of Korea .
Ji Hoon
JH
Jeong
5 Department of Pharmacology, School of Pharmacy, Sungkyunkwan University , Suwon, Republic of Korea .
Choon-Gon
CG
Jang
6 Ginsentology Research Laboratory, Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University , Seoul, Republic of Korea .
Seung-Yeol
SY
Nah
7 Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine , Nagoya, Japan .
Kiyofumi
K
Yamada
8 Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences , Toyoake, Japan .
Toshitaka
T
Nabeshima
9 Headquarters of Forestry Support, Korea Forestry Promotion Institute , Seoul, Republic of Korea .
Jae Kyung
JK
Byun
1 Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University , Chunchon, Republic of Korea .
Hyoung-Chun
HC
Kim