Role of NR2B in estrogen increasing visceral hypersensitivity of female stressed rats / 中华消化杂志

ABSTRACT

Objective As estrogen increases visceral hypersensitivity induced by water avoidance stress in female rats,further experiment was designed to determine whether the influence of estrogen involves NR2B.Methods Healthy adult female Wistar rats were bilaterally ovariectomized,and then housed individually.Implantation of cannula into lateral cerebroventricle and electrodes into the abdominal muscle had been done.After 5 days recovery,rats with abnormal behavior and ehctromyography were excluded,finally a total of 48 rats were eligible,and were equipped for abdominal muscle electromyography and submitted to water avoidance stress(WAS).Visceromotor response(VMR)to 20,40,60 and 80 mmHg colorectal distension(CRD)was recorded in rats intracerebroventricular-infused with either 17β-estradiol,normal saline,AP5(NMDA receptor-antagonist)or Ro25-6981(NR2B antagonist).NR2B mRNA in anterior cingulate cortex or dorsal root ganglia were compared by real-time PCR between the rats treated with 17β-estradioI and that with normal saline.Results Bilaterally ovarieetomized rats treated with 17β-estradiol,exhibited more visceral hypersensitivity after WAS than that with normal saline on 40,60 and 80 mmHg CRD(P=0.039,P=0.033,P=O.001).The VMR on 40 and 60 mmHg CRD in 17β-estradiol treated group was not significantly different from that in 17β-estradiol plus Ro25-6981 treated group.Whilst,significant differences of VMR were noted between 17β-estradiol treated group and 17β-estradiol plus Ro25-6981 treated group on 80 mmHg CRD,17β-estradiol treated group and 17β-estradiol plus AP5 treated group on 60,80 nmmHg CRD,respectively.17β-estradiol increased NR2BmRNA in anterior cingulate cortex(0.57±0.41 vs 0.21±0.13,P=0.048),but not in dorsal root ganglia(0.35±0.45 vs 0.38±0.31,P=0.465). Stress-induced visceral hypersensitivity in the hormonally-restored visceral hyper-responsiveness of bilaterally ovariectomized rats was antagonized by AP5 or Ro25-6981.Conclusions Estrogen may be mediated through NR2B activation to enhance visceral sensitivity in female stressed rats,that probably related with the increased expression of NR2B mRNA in anterior cingulate cortex.