title: Quetiapine add-on therapy improves the depressive behaviors and hippocampal neurogenesis in fluoxetine treatment resistant depressive rats.
abstract: Quetiapine, an atypical antipsychotic, may have efficacy as augmentation therapy in treatment resistant depression (TRD), but evidence is limited and the underlying mechanism remains poorly understood. Therefore, this study was aimed to investigate whether and how quetiapine can be served as an augmentation agent in fluoxetine treatment resistant depressive rats induced by chronic unpredictable mild stress (CUMS). In this study, the effects of CUMS regimen and antidepressant treatment were assessed by behavioral tests and hippocampal neurogenesis. Approximately 20-30% of depressive rats respond poorly to fluoxetine treatment. In their hippocampus, a significant decrease of neurogenesis was also observed. However, quetiapine add-on therapy significantly improved the depressive behaviors and increased the number of the newborn neurons in the hippocampus of fluoxetine treatment resistant depressive rats. Thus, our results suggest that quetiapine may be used as an augmentation agent in the treatment resistant depression partly mediated by increasing the number of newborn neurons in the hippocampus.
authors.affiliation: Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Chang
authors.forename: Yun-Chun
authors.initials: YC
authors.lastname: Chen
authors.forename: Rui-Guo
authors.initials: RG
authors.lastname: Zhang
authors.forename: Hua-Ning
authors.initials: HN
authors.lastname: Wang
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Wu
authors.forename: Zheng-Wu
authors.initials: ZW
authors.lastname: Peng
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Tan
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000963:Antimetabolites; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D003987:Dibenzothiazepines / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D004777:Environment; D005473:Fluoxetine / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D055495:Neurogenesis / Q000187:drug effects*; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000523:psychology; D013395:Sucrose; D013550:Swimming / Q000523:psychology; D016707:Tissue Fixation
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000963:Antimetabolites; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D005473:Fluoxetine; D000069348:Quetiapine Fumarate; D013395:Sucrose; D001973:Bromodeoxyuridine
keywords: Chronic unpredictable mild stress; Hippocampus; Neurogenesis; Quetiapine; Treatment resistant depression