CAJ | 학술논문

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-HTT)和5-羟色胺1A受体(5-HT1AR)机制.方法 150只雄性Sprague-Dawley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-HTT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±5.61,158.65±4.85,且差异均有统计学意义(P＜0.01)；高易感组三个脑区5-HT1AR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±6.05,115.57 ±3.19,且差异有统计学意义(P＜0.01).结论中脑边缘系统VTA-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.
목적 탐토대서만성불가예견성응격(Chronic Unpredictable Stress,CUS)역감성차이적중뇌변연계통5-간색알전운체(5-HTT)화5-간색알1A수체(5-HT1AR)궤제.방법 150지웅성Sprague-Dawley대서이수궤수자표법분위시험조(n=120)화대조조(n=30).실험조건립CUS모형,근거광장시험(Open Field Test,OFT)화강박유영시험(Forced Swimming Test,FST)측평지표장대서분위고、중、저역감조.재응격모형건립후분별처사고、저편애조화대조조대서각8지,원위잡교검측대서내측전액협피질(mPFC)、중뇌복측피개구(VTA)화복격핵(NAc)구5-HTT화5-HT1AR적표체.결과 고역감조삼개뇌구5-HTT적회도치고우저역감조,3조뇌구회도치분별위:mPFC구169.20±8.23,143.53±5.31、Nac구177.41±5.68,158.65±5.24、VTA구174.16±5.61,158.65±4.85,차차이균유통계학의의(P＜0.01)；고역감조삼개뇌구5-HT1AR적회도치저우저역감조,3조뇌구회도치분별위:mPFC구113.98±7.46,125.90 ±3.30、Nac구112.11 ±5.50,125.06±3.97、VTA구103.11±6.05,115.57 ±3.19,차차이유통계학의의(P＜0.01).결론 중뇌변연계통VTA-NAc-mPFC배로중5-HT1AR고표체상태화5-HTT저표체상태여대서CUS고역감성유관.
Objective To investigate the expression of serotonin transporter (5-HTT) 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 susceptibility.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 procedure.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),nucleus 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-HT1AR 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 ; Nac: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-HTT in the circuit of VTA-NAc-mPFC may be the basis of the high susceptibility to CUS.