title: Beneficial effects of EGb761 and vitamin E on haloperidol-induced vacuous chewing movements in rats: Possible involvement of S100B mechanisms.
abstract: Tardive dyskinesia (TD) is a serious side effect induced by the long-term administration of typical antipsychotics. The pathophysiology of TD remains unclear, but experimental evidence suggests that neurodegeneration caused by free radicals may play an important role in TD development. S100B is considered a potential biomarker of structural neural and glial damage. This study investigated S100B expression in TD-related brain regions and assessed the effect of antioxidants Gingko biloba leaf extract (EGb761) and vitamin E (VE) on S100B in TD rats. A total of 32 rats were randomly divided into 4 study groups: saline control (saline), haloperidol alone group (Hal), EGb761-haloperidol (EGb-Hal), and vitamin E-haloperidol (VE-Hal). Rats were treated with haloperidol intraperitoneal injections (2mg/kg/day) each day for 5 weeks. EGb761 (50mg/kg/day) and VE (20mg/kg/day) were then administered during a 5-week withdrawal period. We performed behavioral assessments and immunohistochemically analyzed S100B expression in four TD-related brain regions. Our findings demonstrated that haloperidol administration led to a progressive increase in VCMs and in S100B expression in all four brain regions. Both EGb761 and VE reversed these changes, and there were no group differences between the EGb761 and VE groups. Our results indicated that long-term administration of haloperidol may induce VCMs and increase S100B expression in TD-related brain regions, and S100B may be a significant biomarker related to TD pathophysiology. Moreover, the antioxidant capacity of EGb761 and VE coupled with the possible neuroprotective effects of S100B may account for their success in improving the symptoms of haloperidol-induced TD.
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Institute of Chinese Integrative Medicine, Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
authors.forename: Hui Mei
authors.initials: HM
authors.lastname: An
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Institute of Chinese Integrative Medicine, Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
authors.forename: Yun Long
authors.initials: YL
authors.lastname: Tan
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Institute of Chinese Integrative Medicine, Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Institute of Chinese Integrative Medicine, Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
authors.forename: Zhi Ren
authors.initials: ZR
authors.lastname: Wang
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
authors.forename: Yue Chan
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Institute of Chinese Integrative Medicine, Beijing HuiLongGuan Hospital, Peking University, Beijing, China.
authors.forename: Meng Han
authors.initials: MH
authors.lastname: Lv
authors.affiliation: Institute of Mental Health, Peking University, Beijing, China.
authors.forename: Dong Feng
authors.initials: DF
authors.lastname: Zhou
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Jair C
authors.initials: JC
authors.lastname: Soares
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Thoams R
authors.initials: TR
authors.lastname: Kosten
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Institute of Chinese Integrative Medicine, Beijing HuiLongGuan Hospital, Peking University, Beijing, China. Electronic address: yfd200@126.com.
authors.forename: Fu De
authors.initials: FD
authors.lastname: Yang
authors.affiliation: Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Institute of Chinese Integrative Medicine, Beijing HuiLongGuan Hospital, Peking University, Beijing, China; Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: xiang.y.zhang@uth.tmc.edu.
authors.forename: Xiang Yang
authors.initials: XY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D020441:Ginkgo biloba; D006220:Haloperidol; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D008409:Mastication / Q000187:drug effects* / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010936:Plant Extracts / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*; D000096983:Ginkgo Extract
chemical_list: D018726:Anti-Dyskinesia Agents; D006220:Haloperidol; D010936:Plant Extracts; D064568:S100 Calcium Binding Protein beta Subunit; D014810:Vitamin E; C579158:S100b protein, rat; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract
keywords: Gingko biloba leaf extract; S100B; Tardive dyskinesia; Vitamin E