Increased defecation during stress or after 5-hydroxytryptophan: selectiveinhibition by the 5-HT4 receptor antagonist, SB-207266

1 5-HT4 receptor antagonism prevents the ability of exogenous 5-HT or 5-HTP to sensitize the intestinal peristaltic reflex and increase the rate of de fecation, generally without affecting nonstimulated intestinal function. In this study we confirmed the ability of the selective 5-HT4 receptor antago nist SB-207266 1-1000 mu g kg(-1) p.o., to prevent the increase in defecati on evoked over a 60 min period by 5-HTP 10 mg kg(-1) s.c. in conscious mice , in the absence of an apparent constipating action. 2 The role of endogenous 5-HT in the mechanisms of increased defecation and /or diarrhoea was then investigated in conscious, fed rats. This was evoked by 180 min exposure to restraint stress, which increased both the number a nd mean weight of formed, faecal pellets excreted over the entire time peri od. 3 SB-207266 1-1000 mu g kg(-1) p.o. (dosed 30 min before restraint) did not affect the increase in defecation evoked during the first 60 min of restra int stress, but significantly and dose-dependently reduced or prevented the increased defecation during the remaining 120 min of the experiment; this action occurred in the absence of an apparent constipating action of SB-207 266. 4 In fasted rats exposed to restraint stress, watery diarrhoea developed an d although there was a tendency for SB-207266 1-1000 mu g kg(-1) p.o. (dose d 30 min before restraint) to reduce the incidence of diarrhoea, this inhib ition was not complete. 5 We conclude that selective 5-HT4 receptor antagonism prevents disruptions in defecation behaviours caused by exogenous or endogenous enteric 5-HT an d that this activity is not accompanied by a concomitant suppression of act ivity (constipation-like) within the intestine itself.