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-Teg1.0) 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-Teg1.0)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.Tegasered 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 vs 31±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. AIM: To examine the effects of tegaserod, a serotonin (5-HT) 4 receptor partial agonist, on abdominal withdrawal reflex (AWR) to rectal distention (RD) and c- Fos expression in limbic system. METHODS: Neonatal Sprague-Dawley rats randomlyreceived colonic irritation by acetic acid from postnatal day 8 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 diameter of 2 mm) which was rapidly inflated withincreasing volumes of saline (0.4, 0.8 and 1.2 mL) for 20 sat five-minute intervals. Fleet subgroups of group H (H-saline, H-vehicle, H-Teg0.1, H-Teg0.3 and H-Teg1.0) were injected randomly with saline, vehicle (1-methyl-2-thpyrrolidone) ortegaserod at doses of 0.1, 0.3 and 1.0 mg / kg ip, subgroups of group C (C-Saline and C-Teg1.0) were injected with saline or tegaserod (1.0 mg / kg) ip.RD was formed 10 min after injection, AWR was recorded and c-Fos expression in limbic system was analyzed quantitatively by immunohistochemistry. RESULTS: Compared to saline, tegaserod significantly inhibited 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 had no significant effect on group C. Tegasered dose-dependentlyattenuated the number of c-Fos positive neurons in limbicstructures, anterior cingulate cortex (ACC) showed the greatest 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 vs 31 ± 8, C, tegaserod (1.0 mg / kg) resulted in an overall decrease to 77% of C-saline (214 ± 13 vs 164 ± 22, P <0.01) in ACC to 65% of C-saline (48 ± 8 vs 31 ± 7 , P <0.01). CONCLUSION: Tegaserod inhibits the response to rectaldistention in rats with visceral hypersensitivity and dose-dependently attenuated c-Fos expression in limbic system, especially in anterior cingulate cortex.