title: Upregulating serotonin transporter expression and downregulating monoamine oxidase-A and indoleamine 2, 3-dioxygenase expression involved in the antidepressant effect of sodium valproate in a rat model.
abstract: Sodium valproate (VPA) is widely used as an antiepileptic agent and mood stabilizer. In recent years, VPA has been increasingly used as a psychotherapeutic drug to treat depression. In this article, a possible antidepressant mechanism of VPA was investigated by studying the expression and therefore the involvement of tryptophan hydroxylase, serotonin transporter (5-HTT), monoamine oxidase-A (MAO-A), and indoleamine 2, 3-dioxygenase (IDO) in rats exposed to chronic unpredicted stress. Male Sprague-Dawley rats were divided into four groups: the vehicle-treated control group (CG), the VPA-treated control group (VPAC), the vehicle-treated model group (MG), and the VPA-treated model group (VPAM). VPA (300 mg/kg once daily) was administered to VPAC and VPAM rats by means of intragastric gavage while an equivalent volume of vehicle was given to vehicle-treated CG and MG rats. Rat behavior and expression of tryptophan hydroxylase, 5-HTT, MAO-A, and IDO in the hippocampus were determined. A significant reduction in depression-like behaviors was observed with an upregulation of 5-HTT expression and a downregulation of MAO-A and IDO expression in VPAM rats, compared with MG rats. The results may suggest that the antidepressant mechanism of VPA is partly related to elevated serotonin level and its reuse in the vesicles of presynaptic nerve endings.
authors.affiliation: Departments of aPharmacology bDrug Analysis, Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy of Chongqing Medical University, Chongqing, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Qiu
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Yang
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Jiang
authors.forename: Hui-Zhi
authors.initials: HZ
authors.lastname: Fei
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Hu
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002908:Chronic Disease; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013315:Stress, Psychological; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D014635:Valproic Acid; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase