| Objective:To study the antidepressant-like effect and discuss its possible functi onal mechanism of mice in the model of fluoxetine combined lamotrigine forced st ress and chronic unpredicted mild stress depression.Method:1 The forced stress model in mice:Getting rid of the great difference mice on the basis of the immobility time measurement in the pre-experiment,the remaining mice were randomly and evenly divided:solvent control group,fluoxetine (10 mg/kg)positive drug control group, fluoxetine (10 mg/kg)and lamotrigine (20 mg/kg)combination group.The solvent control group mice were given equivalent dose of 0.5% of sodium carboxymethyl cellulose solution,designed dose of fluoxetine and lamotrigine were given to the other groups,all mice were treated by intragastric adiminstered for seven consecutive days.To evaluate the antidepressant effect of the drug combination,use the immobility time in the tail suspension test and forced swimming test,as well as the rearing and ambulating movement times,the time of staying in center of the open field as the initial screening indicator of antidepressant.2 The chronic stress model in mice:The mice were randomly separated: nonstressed-control group,stressed-control group,fluoxetine group(10 mg/kg), fluoxetine (10 mg/kg) and lamotrigine (10 mg/kg) combination low-dose group and fluoxetine (10 mg/kg) and lamotrigine (20 mg/kg) combination high-dose group.In addition to the normal control group,the remaining four groups of mice were undergoing four weeks of chronic unpredictable mild stress.Eleven kinds of stimulating factor were randomly distributed to seven days a week by random method to build a chronic unpredicted mild stress in mice.After modeling one week of all mice,each group was intragastric administered.Among the groups,the nonstressed-control group didn’t take any drugs.The stressed-control group mice were given equivalent dose of 0.5% of sodium carboxymethyl cellulose solution everyday, pre-experimental-designed dose of fluoxetine and lamotrigine were given to the remaining groups.Each group was intragastric administered continuously for three weeks. To measure and record the body weight of mice on the 0th,7th,14th,21st and 28th day during experiments respectively,in the meantime,rectal temperature measurement and sucrose water intake consumption test were conducted.After the end of modeling,take off the cervical vertebrae to execute of all the mice rapidly and the brain tissue was taken immediately to prepare the corresponding concentration of the tissues’ homogenate in case of the content determination.3 The monoamine neurotransmitter and antioxidant index detection in mice:Detected the content of 5-hydroxytryptamine in the brain tissue of the mice through the enzyme-linked immunosorbent assay combined with inhibiting reuptake of monoamine neurotransmitter norepinephrine test to study the antidepressant mechanism in part of the monoamine neurotransmitter. Study on the antidepressant mechanism in part of the antioxidant system,of which by detecting the content of superoxide dismutase,malondialdehyde and glutathione in the brain tissue of the mice.Results:(1) In the tail suspension test, compared with the solvent control grou p,fluoxetine (10 mg/kg) group and lamotrigine with fluoxetine combination group mice tail suspension immobility time was significantly shortened (P<0.05, P<0.01). In the forced swimming test,compared with the solvent control group, fluoxetine (10 mg/kg) group and drug combination group mice forced swimming immobility time was significantly shortened (P<0.05, P<0.05). In the open-field test, compare d with the solvent control group,fluoxetine (10 mg/kg) group and drug combinatio n group mice had no significant difference (P>0.05) on the rearing and ambulating movement times,the time of staying in center.(2) The effects of drug combination on body weight of CUMS mice by m easurement analysis on the day before molding,the weight of all group mice was same,there was no significant difference(P>0.05).Stressed-control group,fluoxetine (10 mg/kg) group and drug combination groups on the 7th day (the day before ad ministration),the 14th day and the 21st day,compared with the nonstressed-control group, the body weight of mice was significantly lower (P<0.01. P<0.01, P<0.01, P<0.01); On the 28th days of the experiment, compared with the nonstressed-contr ol group, stressed-control group,fluoxetine (10 mg/kg) group and drug combinatio n low-dose group body weight of mice was significantly lower (P<0.01 P<0.01, P<0.01), compared with the stressed-control group, drug combination high-dose gro up body weight of mice was significantly higher (P<0.05).In the CUMS model rectal temperature detection, on the day before molding,the 7th day and the 14th day,the temperature of all group mice was same,there was no significant difference(P>0.05);On the 21st day of experiment,compared with the nonstressed-control group, stressed-control group mice rectal temperature was significantly lower (P<0.01),compared with the stressed-control group, drug combination groups mice rectal temperature was significantly higher (P<0.01, P<0.01); On the 28th day, compared with the nonstressed-control group, stressed-control group mice rectal temperature was significantly lower (P<0.01),compared with the stressed-control group, fluoxetine (10 mg/kg)group mice rectal temperature was significantly higher (P<0.05),and drug combination groups mice rectal temperature was extremely significantly higher,of which had significant statistical significance (P<0.01, P<0.01).In the CUMS model sucrose water intake consumption test,on the 21st day of experiment,compared with the nonstressed-control group,stressed-control group mice absolute sucrose water intake,relative sucrose water intake and sucrose water preference percentage reduced,but there was no significant difference(P>0.05),compared with the stressed-control group,fluoxetine (10 mg/kg) group and drug combination groups absolute and relative sucrose water intake increased,but there was no significant difference(P>0.05),the drug combination low-dose group sucrose water preference percentage was significantly higher (P<0.05); On the 28th day of the experiment, compared with the nonstressed-control group,stressed-control group mice absolute sucrose water intake was significantly lower (P<0.01) and relative sucrose water intake was significantly lower (P<0.05),stressed-control group mice and drug combination high-dose group sucrose water preference percentage was significantly lower(P<0.01),compared with the stressed-control group, fluoxetine (10 mg/kg) group and drug combination groups absolute sucrose water intake significantly increased(P<0.01, P<0.01, P<0.01),fluoxetine (10 mg/kg) group and drug combination low-dose and high-dose group relative sucrose water intake was significantly higher(P<0.05, P<0.01),fluoxetine (10 mg/kg) group and drug combination group sucrose water preference percentage was significantly higher(P<0.01, P<0.01, P<0.01).(3) In the inhibiting reuptake of monoamine neurotransmitter norepinephrine test, compared with the solvent control group,the mortality of fluoxetine (10 mg/kg) group mice had a slightly higher,but there was no significant difference(P>0.05),the mortality of drug combination group was significantly higher(P<0.05). The levels of monoamine neurotransmitter 5-hydroxytryptamine in brain tissue detection showed:compared with the nonstressed-control group,stressed-control group and fluoxetine (10 mg/kg) group and drug combination low-dose group 5-hydroxytryptamine content was significantly lower(P<0.01, P<0.01, P<0.01); Compared with the stressed-control group, fluoxetine (10 mg/kg) group, drug combination low-dose and high-dose group 5-hydroxytryptamine content was significantly higher(P<0.05, P<0.05, P<0.01).In the part of antioxidant system,the content detection results of superoxide dismutase,malondialdehyde and glutathione in the brain tissue of the mice showed:compared with the nonstressed-control group,stressed-control group SOD content was significantly lower(.P<0.05), MDA content was significantly higher(P<0.05), GSH content was significantly lower(P<0.05);Compared with the stressed-control group,the drug combination high-dose group SOD content was significantly higher(P<0.01), the drug combination high-dose group MDA content was significantly lower(P<0.05),the drug combination groups GSH content was significantly higher(.P<0.01, P<0.01).Conclusion:Fluoxetine in conjunction with lamotrigine could significantly improve depressive behavior in mice,its antidepressant-like mechanism may be related at least in part to the levels of monoamine neurotransmitters 5-hydroxytryptamine as well as norepinephrine and the balance of the oxidative stress system in the brain tissue. |
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