Observation On The Therapeutic Effect Of Small Dosage Of Ketamine To Treat Depression And Its Mechanism

Depression is a common mood disorder which is characterized by reduced interest and even extreme negative perceptions and suicidal behaviors.Similarly,the mortality incidence of depression is very high.It estimates that depression will become the world's second most common diseases by 2020^[1].Mounting studies have demonstrated that the pathogenesis of depression may be associated with abnormalities in expression of neurotrophic factors and pro-inflammatory cytokines^[2-4].However,many studies suggest that ketamine has potential to alleviate depression symptoms quickly^[5,6].This study aimed to using animal experiments and clinical trials to explore the effect of ketamine on depression,and try to elucidate its therapeutic mechanisms,thereby providing theoretic basis for clinical application.1.Effects of ketamine on the expression of IL-1?and IL-6 in mentally depressed rats.Objective To observe the effects of ketamine on the expression of interleukin-1??IL-1??and interleukin-6?IL-6?in prefrontal cortex and hippocampus in mentally depressed rats.Methods Twenty male Wistar rats weighing 180-220 g were randomly divided into 2 groups?n=10 each?:saline?group C?and ketamine 10 mg/kg?group K?.The forced swimming test?FST?of 15 min was used to establish a rat depression model.On the 2nd day,group C and group K were intraperitoneally injected,respectively.Thirty minutes later,the FST of 5 min was used and the rat immobility time during FST was recorded.The prefrontal cortex and hippocampus were harvested for determination of IL-1?and IL-6 levels.Results Compared with group C,rats in Group K showed significant decrease in the immobility time of forced swimming test?p<0.01?and the expression of IL-1?and IL-6 in prefrontal cortex and hippocampus?p<0.05?.Conclusion Ketamine exerting antidepressant effects in the forced swimming test may be associated with the down-regulation of IL-1?and IL-6 in rat prefrontal cortex and hippocampus.2.Effects of ketamine on serum BDNF and 5-HT levels in patients with depression.Objective To explore a single small dose of intravenous ketamine on depression and serum brain derived neurotrophic factor?BDNF?and 5-hydroxytryptamine?5-HT?levels in patients with depression.Methods Thirty-nine patients with depression according to admission principle,and were randomly divided into two groups:control group?n=20?and ketamine group?n=19?.Ketamine group was administered with 0.5mg/kg ketamine in 50 ml saline,the control group was administered equal volume of saline.Before treatment and 1,3,7 d after treatment,Hamilton Depression Scale?HAMD?was performed and peripheral blood samples were collected by measurement of serum levels of BDNF and 5-HT in.Results Compared with the control group,HAMD score in ketamine group was significantly decreased?p<0.05?,but the peripheral level of BDNF1 day after treatment was significantly increased?p<0.01?.Although the BDNF level was slightly decreased during 3 days after treatment,its level was also significantly increased as compared with those in control group?p<0.05?.On day 7,there is,however,no significant difference?p>0.05?.5-HT levels at all the time points showed no significant difference between the two groups?p>0.05?Conclusion The antidepressant effect of ketamine may be associated with the up-regulation of the expression of BDNF.However,further detailed studies on the role of 5-HT in ketamine exerting therapeutic effects for depression are required.