title: Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice.
abstract: BACKGROUND
  Clinical studies demonstrate that the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, induces rapid antidepressant effects in patients with refractive major depressive disorder and bipolar depression. This rapid onset of action makes ketamine a highly attractive drug for patients, particularly those who do not typically respond to therapy. A recent study suggested that glycogen synthase kinase (GSK)-3 may underlie the rapid antidepressant action of ketamine, although the precise mechanisms are unclear. In this study, we examined the effects of ketamine and GSK-3 inhibitor SB216763 in the unpredictable, chronic mild stress (CMS) mouse model of mice.
  
  
  RESULTS
  Adult C57/B6 male mice were divided into 2 groups, a non-stressed control group and the unpredictable CMS (35 days) group. Then, either vehicle, ketamine (10 mg/kg), or the established GSK-3 inhibitor, SB216763 (10 mg/kg), were administered into mice in the CMS group, while vehicle was administered to controls. In the open field test, there was no difference between the four groups (control+vehicle, CMS+vehicle, CMS+ketamine, CMS+SB216763). In the sucrose intake test, a 1% sucrose intake drop, seen in CMS mice, was significantly attenuated after a single dose of ketamine, but not SB216763. In the tail suspension test (TST) and forced swimming test (FST), the increased immobility time seen in CMS mice was significantly attenuated by a single dose of ketamine, but not SB216763. Interestingly, the ketamine-induced increase in the sucrose intake test persisted for 8 days after a single dose of ketamine. Furthermore, a single administration of ketamine, but not SB216763, significantly attenuated the immobility time of the TST and FST in the control (non-stressed) mice.
  
  
  CONCLUSIONS
  These findings suggest that a single administration of ketamine, but not GSK-3 inhibitor SB216763, produces a long-lasting antidepressant action in CMS model mice.
authors: Department of Psychiatry, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xian, China.
authors: Xian-Cang
authors: XC
authors: Ma
authors: Yong-Hui
authors: YH
authors: Dang
authors: Min
authors: M
authors: Jia
authors: Rui
authors: R
authors: Ma
authors: Fen
authors: F
authors: Wang
authors: Jin
authors: J
authors: Wu
authors: Cheng-Ge
authors: CG
authors: Gao
authors: Kenji
authors: K
authors: Hashimoto
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019417:Hindlimb Suspension; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects*; D013395:Sucrose / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C417521:SB 216763; D013395:Sucrose; D007649:Ketamine; D038362:Glycogen Synthase Kinase 3
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