Involvement of the 5-HT₃ receptor in CRH-induced defecation in rats

We evaluated the possibility that serotonin (5-HT) mediates defecation induced by corticotropin-releasing hormone (CRH) exogenously administered or released from the central nervous system by stress via the 5-HT₃ receptor in rats. Intracerebroventricular (ICV) injection of CRH (1, 3, and 10 μg/rat) dose dependently increased the number of stools excreted in rats, whereas intravenous (IV) injection of up to 100 μg/kg CRH did not affect defecation. α-Helical CRH-(941) and 5-HT₃ receptor antagonists ramosetron and azasetron inhibited CRH (10 μg icv)-induced defecation in a dose-dependent manner with ED₅₀ values of 4.3 μg/kg iv, 3.8 μg/kg po, and 70.4 μg/kg po, respectively. α-Helical CRH-(941) also inhibited CRH-induced defecation by ICV injection with an ED₅₀ value of 0.078 μg/rat. In contrast, ramosetron and azasetron injectied ICV had no effect on CRH-induced defecation. α- Helical CRH-(941), ramosetron, and azasetron reduced defecation caused by restraint stress with ED₅₀ values of 0.32, 3.6, and 19.7 μg/kg iv, respectively. These results indicate that CRH exogenously administered or released from the central nervous system by stress peripherally promotes the release of 5-HT, which in turn stimulates defecation through the 5-HT₃ receptor.