Chronic Unpredictable Stress In The Effect Of Dopamine D2 Receptor MRNA Expression Of Reward-loop

Background:Reward-loop is one part of the brain limbic system, which is made of midbrain ventral tegmental area, ventral striatum, bed nucleus of the stria terminalis, hippocampus, amygdala, septal area, and its main neurotransmitter is dopamine. Normal reward effect is the prerequisite for the body to adjust to the external environment, maintain body ingestion and sexual activities. The main research of the reward loop (DA channel) in the past focused on substance abuse while the study of depression mainly focused on the 5-HT and NE function in the hippocampus and striatum; apparently such kind of division is man-made. Depression symptoms, such as deletion of pleasure, psychic physical retardation, may be associated with the moderation of the reward system (DA) within the central neural system. Therefore, recently the effects of reward loop in depression begin to gain more attention and further studies mainly focus on loss of interests and DA system dysfunction in order to support the depression therapy theoretically.Objective:we use long-term variety of chronic unpredictable mild stress combine to Solitary support to establish the mouse model of depression, then we observe and analyze the change of body weight, sucrose intake, and behavioral, and to explore chronic unpredictable mild stress in the effect of dopamine D2 receptor mRNA expression of reward-loop in the mice.Methods:16 mice, body weight (20±2) g, were randomly divided into control group and the chronic stress group n= 8; the control group does not impose any stimulation, Chronic stress group alone raised by sub-cage, and put in 21 days,7 kinds of random stimulation. Before the start of the experiment, one week, two weeks, three weeks (stress began on day 0,7 days,14 days and 21 days) per mouse was measured body weight, sugar intake and sugar consumption index. Application of forced swimming test and sugar consumption to test behavior changes.the last, we detecte dopamine D2 receptor gene expression levels by RT-PCR in brain septal area and midbrain ventral tegmental area.Results:1. The effect of CUMS model to body weight:before the experiment, there is no obvious difference of rats in blank and stimulus group in weights(blank:20.00±1.60, stimulus:20.13±1.64,p> 0.05). On the seventh, fourteenth and twenty-first day after the stimulus, the rat weights in the stimulus group(26.63±2.20,31.00±2.78,33.86±1.46) are significantly less than those in the blank group(29.00±1.31,34.50±2.78,37.88±1.96), with remarkable difference.2. CUMS model forced swimming test:before the experiment, there is no obvious difference of rats in blank and stimulus group in swimming test static time(blank:104.00±13.52 s, stimulus:99.38±15.12 s, P>0.05) while after the stimulus compared to the blank group(101.88±11.05 s), the swimming test static time of the rats in the stimulus group extends distinctly (p<0.01).3. CUMS model of sugar consumption test:before the experiment, there are no obvious differences of rats in blank and stimulus group in sucrose consumption, pure water consumption, gross consumption and sucrose preference index (blank:2.99±0.43 g,0.80±0.21 g,3.79±0.33 g,78.47±6.54%, stimulus:3.17±0.61 g,0.88±0.47 g,4.05±0.29 g,77.90±11.99%, p>0.05) while after the stimulus, there are obvious differences(blank:2.86±0.49 g,0.89±0.33 g,3.74±0.77 g,76.81±4.56%, stimulus:1.32±0.38 g, 1.58±0.50 g,2.90±0.37 g,46.19±13.59%, p<0.01).4. There is remarkable difference in the aspect of dopamine D2 receptor expression in the septal area and ventral striatum of rats in blank and stimulus group (blank:0.792±0.111,0.843±0.181, stimulus:1.204±0.354,1.181±0.265,p<0.01).Conclusion:1.Chronic mild unpredictable stimulus-reaction can build up rat depression mode successfully and the accumulation effect of mild stimuli can make rats depressed.2. The weight growth of the rats in chronic stimulus-reaction group is obviously slowed down.3. The sucrose preference index in the sucrose consumption test of the rats in chronic stimulus-reaction group is remarkably lower.4. The swimming test static time in 5mins of the rats in chronic stimulus-reaction group is prolonged notably.5. Chronic unpredictable stimulus-reaction can restrain the expression of the Reward Loop Dopamine D2 Receptor.