| Objective:With more and more life stress induced by the accelerated pace of modern life, the incidence of depression has showed an increasing trend, which inspires people to explore the pathogenesis of depression. We established the chronic unpredictable stress model rats. Carbon fiber electrode measurement technique was used to detect the release of serotonin in prelimbic cortex induced by electrical stimulation of dorsal raphe nucleus of rats. We observed the effects of administrating 5-HT1A receptor agonist and 5-HT2A receptor agonist on 5-HT stimulation-secretion, in order to probe into the cellular and molecular mechanisms of chronic unpredictable stress leading to the change of 5-HT secretion in prelimbic cortex, and provide experimental evidence for the pathogenesis of depression.Methods:70 clean grade male Sprague-Dawley (SD) rats (180-200g) were divided in two rounds experiments depending on injection drugs.35 rats in each round experiment were randomly divided into control group (n=16) and model group (n=19) based on body weight. Depression model rats were established by applying combination of chronic unpredictable stress and solitary living. The body weight, open-field test score, the percent of sugar water consumption, blood pressure and heart rate were detected before and after modeling in each of the two groups’rats. After the end of modeling,5-HT release in the prelimbic cortex induced by electrical stimulation in dorsal raphe nucleus (DRN) was recorded by carbon fiber electrode. The peak value, the time to peak and half-life period of 5-HT signal in both group rats were analyzed. Two groups of rats were intraperitoneal injection with 5-HT1A receptor agonist 8-OH-DPAT in the first round of experiments.5-HT2A receptor agonist DOI was administrated intracerebroventricularly to two groups of rats in the second round of experiments.Results:After 21 days chronic unpredictable stress, the body weight of model group rats was significantly lower than the control group (271.7±23.7 g, n= 19 vs 334.3±37.8 g, n=23, P<0.001); The open-field test level score (7.5±6.6, n=19 vs 25.6±9.6, n=23,P<0.001), vertical score (4.2±2.9, n=19 vs 9.9±4.8, n=23,P <0.001) and total score (11.6±9.1,n 19 vs 35.5±13.7, n=23,P<0.001) were lower in the model group; and the percentage of sugar consumption in model rats also lower (47.2%±17.4%, n= 19 vs 66.1%±17.8%, n=23,P<0.05), but no significant difference was observed in blood pressure and heart rate.In vivo electrical stimulation of dorsal raphe nucleus, the release of the neurotransmitter 5-HT in the prelimbic cortex was detected by using carbon fiber electrode recording technique. The peak value, the time to peak and half-life period of 5-HT signal had not statistically difference between the two group rats.After intraperitoneal injection with 8-OH-DPAT (lmg/kg) for 30min, the peak value of 5-HT signal was decreased in model group rats (97.7±65.3 pA vs 183.6±105.6 pA, n=10,P<0.05) and control group rats (101.4±83.8 pA vs 236.5±119.4 pA, n=13, P<0.001). The half-life period in the control group 5-HT signal was shorter (1.8±1.5 s vs 4.2±2.4 s, n=13, P<0.05) but had no significant differences in model group rats. The time to peak had no significant change in both group rats.After intracerebroventricular injection of DOI(20 μ g) for 30 minutes,5-HT release was inhibited in model group rats(133.6±82.5 pA vs 232.2±105.0 pA, n=9, P<0.01)and in control group rats (107.6±77.7 pA vs 293.1±163.8 pA, n=10, P<0.01). The time to peak and half-life period of 5-HT signal had no significant change in both group rats.Conclusion:1. Chronic unpredictable stress combined with separation raising can produce a stable depressive-like behavior model rats.2. The 5-HT secretion in the PrL can be detected by carbon fiber electrode when the DRN is electrically stimulated in vivo. The peak value, the time to peak and the half-life period of the 5-HT signal have no statistical difference between the depression model group rats and the control group rats.3.5-HT1A receptor agonist 8-OH-DPAT can inhibit the secretion of 5-HT in the PrL induced by electrical stimulation in the DRN of the rats.4.5-HT2A receptor agonist DOI can inhibit the secretion of 5-HT in the PrL induced by electrical stimulation in the DRN of the rats. |
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