AIM: To examine the effects of tegaserod, a serotonin(5-HT) 4 receptor partial agonist, on abdominal withdrawalreflex (AWR) to rectal distention (RD) and c-Fos expressionin limbic system.METHODS: Neonatal Sprague-Dawl...AIM: To examine the effects of tegaserod, a serotonin(5-HT) 4 receptor partial agonist, on abdominal withdrawalreflex (AWR) to rectal distention (RD) and c-Fos expressionin limbic system.METHODS: Neonatal Sprague-Dawley rats randomlyreceived colonic irritation by acetic acid from postnatal day8 to d 21 as a visceral hypersensitive model (group H) or byintrarectal saline as a control group (group C). When theybecame adults, rectal distention (RD) was performed by aballoon (6F; Fogarty arterial embolectomy catheter; length,20 mm; diameter, 2 mm) which was rapidly inflated withincreasing volumes of saline (0.4, 0.8 and 1.2 mL) for 20 sat five-minute intervals. Five subgroups of group H (H-saline,H-vehicle, H-Teg0.1, H-Teg0.3 and H-Tegl.0) were injectedrandomly with saline, vehicle (1-methyl-2-thpyrrolidone) ortegaserod at doses of 0.1, 0.3 and 1.0 mg/kg ip, respectively.Two subgroups of group C (C-Saline and C-Tegl.0) wereinjected with saline or tegaserod (1.0 mg/kg) ip. RD wasperformed 10 rain after injection, AWR was recorded andc-Fos expression in limbic system was analyzed quantitativelyby immunohistochemistry.RESULTS: Compared to saline, tegaserod significantlyinhibited AWR in group H (0.4 mL: from 2.0 to 0.5; 0.8 mL:from 3.5 to 1.5; 1.2 mL: from 4.0 to 3.0, P<0.01), but hadno significant effect on group C. Tegaserod dose-dependentlyattenuated the number of c-Fos positive neurons in limbicstructures, anterior cingulate cortex (ACC) showed thegreatest attenuation. In group H, tegaserod (1.0 mg/kg)resulted in a significant overall decrease to 57% of H-saline(283+41 vs 162+16, P<0.01), in ACC to 42% of H-saline(72+10 vs31+8, P<0.01). In group C, tegaserod (1.0 mg/kg)resulted in an overall decrease to 77% of C-saline (214+13vs 164+22, P<0.01), in ACC to 65% of C-saline (48+8 vs31+7, P<0.01).CONCLUSION: Tegaserod inhibits the response to rectaldistention in rats with visceral hypersensitivity and dose-dependently attenuates c-Fos expression in limbic system,especially in anterior cingulate cortex.展开更多
文摘AIM: To examine the effects of tegaserod, a serotonin(5-HT) 4 receptor partial agonist, on abdominal withdrawalreflex (AWR) to rectal distention (RD) and c-Fos expressionin limbic system.METHODS: Neonatal Sprague-Dawley rats randomlyreceived colonic irritation by acetic acid from postnatal day8 to d 21 as a visceral hypersensitive model (group H) or byintrarectal saline as a control group (group C). When theybecame adults, rectal distention (RD) was performed by aballoon (6F; Fogarty arterial embolectomy catheter; length,20 mm; diameter, 2 mm) which was rapidly inflated withincreasing volumes of saline (0.4, 0.8 and 1.2 mL) for 20 sat five-minute intervals. Five subgroups of group H (H-saline,H-vehicle, H-Teg0.1, H-Teg0.3 and H-Tegl.0) were injectedrandomly with saline, vehicle (1-methyl-2-thpyrrolidone) ortegaserod at doses of 0.1, 0.3 and 1.0 mg/kg ip, respectively.Two subgroups of group C (C-Saline and C-Tegl.0) wereinjected with saline or tegaserod (1.0 mg/kg) ip. RD wasperformed 10 rain after injection, AWR was recorded andc-Fos expression in limbic system was analyzed quantitativelyby immunohistochemistry.RESULTS: Compared to saline, tegaserod significantlyinhibited AWR in group H (0.4 mL: from 2.0 to 0.5; 0.8 mL:from 3.5 to 1.5; 1.2 mL: from 4.0 to 3.0, P<0.01), but hadno significant effect on group C. Tegaserod dose-dependentlyattenuated the number of c-Fos positive neurons in limbicstructures, anterior cingulate cortex (ACC) showed thegreatest attenuation. In group H, tegaserod (1.0 mg/kg)resulted in a significant overall decrease to 57% of H-saline(283+41 vs 162+16, P<0.01), in ACC to 42% of H-saline(72+10 vs31+8, P<0.01). In group C, tegaserod (1.0 mg/kg)resulted in an overall decrease to 77% of C-saline (214+13vs 164+22, P<0.01), in ACC to 65% of C-saline (48+8 vs31+7, P<0.01).CONCLUSION: Tegaserod inhibits the response to rectaldistention in rats with visceral hypersensitivity and dose-dependently attenuates c-Fos expression in limbic system,especially in anterior cingulate cortex.
