| Objective: Depression is the main mental disease of human beings.Transcranial direct current stimulation(t DCS)is a non-invasive technique that regulates the activity of cerebral cortical neurons.In this study,t DCS was used to treat depressive rats.Behavioral changes and the dynamics of NE release in hypothalamus of depressive rats was observed before and after t DCS treatment with different parameters,so as to explore the central nervous system mechanism of t DCS to treat depression.Methods: 88 male clean SD rats(180-200g)were divided into two groups with 44 rats in each round.According to the total score of open field experiment,they were divided into control group and model group.The control group consisted of 10 rats,which were divided into 5 anesthetic control group and 5 blank control group.There were 10 pseudo-t DCS rats in the model group,10 in the model group with short-term t DCS(2m A/30min)and 10 in the model group with long-term t DCS(2m A/30min/4 days/twice a day).The percentage of sugar and water consumption experiment,the total score of open field experiment,body weight,blood pressure and heart rate were monitored before modeling in the control group and model group.After 21 days of chronic unpredictable stimulation,the percentage of sugar consumption experiment,the total score of open-field experiment,body weight,blood pressure,heart rate were also monitored.In the treatment of depression with t DCS,the anode was placed in the left prefrontal cortex and the cathode was placed in the right prefrontal cortex.At the end of the modeling,the release kinetics of norepinephrin(NE)in hypothalamus of rats was monitored in vivo by carbon fiber electrode technology with locus coeruleus nucleus stimulation in vivo.The peak value,peak time and half-life of NE secretion signal in hypothalamus before and after pseudo-t DCS or t DCS were recorded.Results: 21 days of chronic unpredictable stimulation reduced the percentage of sugar preference(before modeling 73%±13%,n = 20 vs after modeling 41%±16%,n = 20,P < 0.01)and the total score of open-field experiment in rats of model group(before modeling 46.2±14.2,n = 20 vs after modeling 11.8±10.6,n = 20,P < 0.01).Compared with the control group,the peak value of NE release signal in hypothalamus reduced in the model group(275.2±99.5,n = 12 vs 160.9±31.9,n = 11,P < 0.05).There was no significant difference in peak time(1.63±0.7,n = 12 vs 1.73±0.47,n = 11,P > 0.05)and half-life(7.9±5.0,n=12 vs 5.6±2.4,n=11,P >0.05)between the control group and the model group.There was no significant difference in the peak value of NE release signal in hypothalamus before and after pseudo t DCS in model group(120±47.5,n=7 vs 117±50.5,n=7,P >0.05).There was no significant difference in the time to peak(1.2±0.48,n = 7 vs 1.36±0.26,n = 7,P > 0.05)and the half-life of NE release from hypothalamus(6.14±0.45,n = 7 vs 8.32±6.1,n = 7,P > 0.05)before and after pseudo t DCS in model group.In model group,the peak value of NE release signal in hypothalamus was increased after short-term t DCS(2m A/30min)(before t DCS 99.5±31.9,n=11 vs after t DCS 231±104.6,n=11,P < 0.05).The time to peak(1.7±0.5,n=11 vs 2.5±3.4,n=11,P >0.05)and the half-life(5.6±2.4,n=11 vs 12.9±11.4,n=11,P >0.05)of NE release signal in hypothalamus of model group had no statistical difference before and after in vivo short-term t DCS(2 m A/30 min).There was no significant difference in the peak value(324.8±35.8,n=4 vs 231±104.6,n=11,P > 0.05),the time to peak(control group vs model group 1.7±0.6,n = 4 vs 1.6±0.4,n = 11,P > 0.05)and the half-life(control group vs model group 5.5±4,n = 4 vs 12.9±11.4,n = 11,P > 0.05)of NE release signal in hypothalamus between control group and short-term t DCS(2 m A/30 min)model group after short-term t DCS(2 m A/30 min)in vivo in both groups.There was no significant difference in the percentage of preference for sugar water(59%±16%,n=9 vs 59%±17%,n=14,P >0.05)and the total score of open field experiment(35.9±8.1,n = 9 vs 31.4±10.5,n = 14,P > 0.05)between the control group and the model group stimulated by long-term t DCS(2 m A/ 30 min/ twice a day,4h intervals/ lasting for 4 days).The percentage of preference for sugar water(45%±18%,n=14 vs 59%17%,n=14,P < 0.05)and the total score of open-field test(16.9±16.4,n=13 vs 31.4±10.5,n=14,P < 0.05)were increased before and after long-term t DCS(2 m A/30 min/twice a day,4h intervals/ lasting for 4 days)in the model group.There was no significant difference in the peak value(235.7 + 79.4,n = 7 vs 361.4 + 201.5,n = 7,P > 0.05),the time to peak(1.78±0.36,n=7 vs 1.44±0.29,n=7,P >0.05)and the half-life(11.4±10.4,n= 7 vs 9.0 ±5.3,n = 7,P > 0.05)of NE release in hypothalamus between before and after t DCS of 2 m A/30 min in vivo in the model group rats treated with long-term t DCS(2 m A/30 min/twice a day,4h intervals/ lasting for 4 days).There was no significant difference in the peak value of NE release signal in hypothalamus between control group and model group after long-term t DCS(2 m A/30 min/twice a day,4h intervals/ lasting for 4 days)(229.8+140.6,n=4 vs 235.7+79.4,n=7,P>0.05).The time to peak was increased in the model group(1.2 + 0.2,n = 4 vs 1.8 + 0.4,n = 7,P < 0.05).The half-life was increased in model group(2.7 + 0.7,n = 4 vs 11.4 + 10.4,n = 7,P < 0.05).Conclusion: 1.Chronic unpredictable stress combined with solitary rearing can make a stable depression rat model.2.Long-term t DCS(2 m A/30 min/twice a day,4h intervals/ lasting for 4 days)can treat depressive rats.3.In vivo t DCS can increase NE secretion in hypothalamus of depression rats.4.NE secretion in hypothalamus of depression rats can be increased by t DCS treatment.5.t DCS can improve the depression-like behavior of chronic unpredictable stress model rats,which is related to the increase of NE secretion in the hypothalamus by stimulating locus coeruleus project system. |
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