| Objective: To investigate the effects of ketamine,imipramine,and ketamine plus imipramine on chronic depression-like behaviors,as well as the expression of β form calcium/calmodulin-dependent protein kinase type(ⅡβCaMKⅡ)in the habenula,and membrane fraction of glutamate receptor1(GluR1)in the habenula and the prefrontal cortex in Wistar Kyoto(WKY)rats.Methods: Randomly grouped rats were treated with saline i.p.for 2 weeks,ketamine i.p.in week 1 but with saline in week 2,imipramine i.p.for 2 weeks,and ketamine i.p.in week 1 and saline in week 2 plus imipramine i.p.for 2 weeks,respectively.The depression-like behaviors were assessed by the sucrose preference test and the forced swimming test.The expressions of βCaMK Ⅱand GluR1 were measured in corresponding brain tissue with western blot analysis.Results: 1)Imipramine and ketamine plus Imipramine Group treatments significantly decreased the immobility time when compared with saline treated group,while ketamine treated group showed no obvious effect.In sucrose preference test,however,all three therapeutic schedules had no effects.2)Imipramine treatment and ketamine plus imipramine treatment,but not ketamine treatment,significantly decreased the expression of βCaMK and GluⅡR1 in habenula of WKY rats.The expression of GluR1 significantly increased in the prefrontal cortex in all treatment groups.Conclusion: Imipramine treatment(2 weeks)significantly improved depression like behaviors in WKY rats,and the application of ketamine in the first week has no reinforcing effect on imipramine treatment at the end of the second week.The mechanisms underlying the anti-depressive effect of imipramine may be associated with the down-regulation of βCaMK Ⅱand membrane GluR1 in the habenula and the up-regulation of GluR1 in prefrontal cortex. |
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