Study Of Dorsal Raphe Nucleus Secretion In Chronic Unpredictable Stress Model Rats

Objective: Stress event is one of the important factors that lead to depression. Chronicunpredictable stress animal models are widely used in depression research. Centralmonoamine neurotransmitters (5-HT, NE, DA) system disorder is one of the mostimportant mechanisms of depression. Dorsal raphe nuclei (DRN) located in brain stemproject5-HTnergic axons to almost all regions of brain. The prelimbic cortex in ratbelongs to the prefrontal cortex which involves with higher brain function such asemotion, learning and memory, motivation. Since it is few reported whether5-HTsecretion changes in prelimbic cortex in chronic unpredictable stress model, the projectwas designed to study5-HT release in the prelimbic cortex followed by electricalstimulation dorsal raphe nuclei in vivo in chronic unpredictable stress model in rats.Methods: To establish chronic unpredictable stress rat model of depression, SD rats(180-200g) suffered7different stress stimulations randomly during21modeling days.Open field test and1%sucrose solution consumption had been measured to determinewhether the modeling was success. Body weight, blood pressure and heart rate also bemeasured in waking rats to observe the autonomic system. Monoamine neurotransmitterrelease in anesthesia rats were recorded by the carbon fiber electrode technique. Thepeak value、time to peak and half-time of peak value in secretion signal were analyzed.Results: The open field test scores of model group rats are significantly lower thancontrol group (24.4±6.9vs.66.6±12.0, n=10,P<0.001), sugar consumption and thepercentage of sucrose preference are significantly lower than those in the control group (3.1±2.5g vs.9.6±5.1g,46.2±25.4%vs.67.3±15.0%respectively, n=10, P<0.05),the body weight of the model rats are significantly lower than the control group (274.2±21.3g vs.348.8±22.2g, n=10, P<0.001). These data can prove the depression rat modelis successful. But5-HT release in prelimbic cortex followed by stimulation of the dorsalraphe nucleu had no significant difference between the model group (n=5) and thecontrol group (n=8) rats in this study. Intraperitoneal injection of5-HT2Areceptorantagonist ketanserin2mg/kg significantly increased5-HT release peak in control grouprats (312.8±87.8pA vs.159.0±60.8pA, n=8, P<0.05). Intraperitoneal injection of5-HT1Areceptor antagonist NAN-190(5mg/kg) had no effect on5-HT secretion signalin depression model group (n=5) rats.Conclusion: Chronic unpredictable stress stimulation can produce the animal models ofdepression.5-HT2Areceptor antagonist ketanserin increases the release of serotonin inprelimbic cortex followed by electrical stimulating dorsal raphe nucleus.