慢性不可预见性应激易感性差异的5-羟色胺转运体和5-羟色胺受体机制研究  

Mechanisms of serotonin transporter and serotonin IA receptor in the different susceptibility of chronic unpredictable stress

作　　者：刘杰[1] 王瑛[2] 贾梅志[3] 王晓慧[2] 张尚荣[2] 尚士渲[2] 

机构地区：[1]中国人民解放军第261医院精神四科,北京100094 [2]中国人民解放军第261医院心理科,北京100094 [3]中国人民解放军第261医院精神一科,北京100094

出　　处：《中华行为医学与脑科学杂志》2013年第2期113-115,共3页Chinese Journal of Behavioral Medicine and Brain Science

摘　　要：目的探讨大鼠慢性不可预见性应激（Chronic Unpredictable Stress，cus）易感性差异的中脑边缘系统5-羟色胺转运体（5-Hrrr）和5-羟色胺lA受体（5-HT1AR）机制。方法150只雄性Sprague—Daw—ley大鼠以随机数字表法分为试验组（n=120）和对照组（n=30）。实验组建立CUS模型，根据旷场试验（Open Field Test，OFT）和强迫游泳试验（Forced Swimming Test，FST）测评指标将大鼠分为高、中、低易感组。在应激模型建立后分别处死高、低偏爱组和对照组大鼠各8只，原位杂交检测大鼠内侧前额叶皮质（mPFC）、中脑腹侧被盖区（VTA）和伏隔核（NAc）区5-HT1A和5-HT1AR的表达。结果高易感组三个脑区5-HTT的灰度值高于低易感组，3组脑区灰度值分别为：mPFC区169．20±8．23，143．53±5．31、Nac区177．41±5．68，158．65±5．24、VTA区174．16±5．61，158．654±4．85，且差异均有统计学意义（P〈0．01）；高易感组三个脑区5-HTlAR的灰度值低于低易感组，3组脑区灰度值分别为：mPFC区113．98±7．46，125．90±3．30、Nac区112．11±5．50，125．06±3．97、VTA区103．11±6．晒，115．57±3．19，且差异有统计学意义（P〈0．01）。结论中脑边缘系统VrA—NAc-mPFC环路中5-HT1AR高表达状态和5-HTT低表达状态与大鼠CUS高易感性有关。Objective To investigate the expression of serotonin transporter （5-HTr） and serotonin 1A treceptor （ 5-HT1 A R） located in the chronic unpredictable stress （ CUS ） -relative brain areas （ mPFC, VTA, NAc ） in high and low CUS susceptibility rats, thus to unveil the possible mechanism lead to the different CUS susceptibil-ity. Methods One hundred and fifty male Sprague-Dawley rats were randomly assigned into experiment group （ n = 120） and control group （ n = 30）. Rats in experiment group were trained according to established CUS proce-dure. OFT and FST were used to assess the different susceptibility to CUS： high susceptibility group （H group） and low susceptibility group （L group）. After the model was established,rats were scarified and cardio-perfused, and the brains were removed and sliced up coronarily. The sections including ventral tegmental area （VTA） , nu-cleus accumben （ NAc ） , medial prefrontal cortex （ mPFC ） were selected. The mRNA levels of 5-HTT and 5-HT1AR in the regions were estimated with in situ hybridization. Results The expression of 5-HTT in H group were significantly lower than that of in the control and L group in all regions （ mPFC ： 169.20 ± 8.23 vs 143.53 ± 5.31 ;Nac：177.41 ±5.68 vs 158.65 ±5.24;VTA：174.16 ±5.61 vs 158.65 ±4.85）,and the difference between the H and L group was significant （P 〈 0.01 ） ;however, the expression of 5-HT1 A R in H group were significantly higher than that of in the control and L group in all regions （ mPFC ： 113.98 ± 7.46 vs 125.90 ± 3.30 ; Nae ： 112.11 ± 5.50 vs 125.06 ± 3.97 ; VTA ： 103.11 ± 6.05 vs 115.57 ± 3.19 ）, and the difference between the H and L group was significant （P 〈 0.01 ）. Conclusion The overexpression of 5-HT1AR and down regulation of 5-HTF in the circuit of VTA-NAc-mPFC may be the basis of the high susceptibility to CUS.

关 键 词：慢性不可预见性应激 5-羟色胺转运体 5-羟色胺1A受体 

分 类 号：R74[医药卫生—神经病学与精神病学]