Restraint stress stimulates colonic motility via central corticotropin-releasing factor and peripheral 5-HT3 receptors in conscious rats

Although restraint stress accelerates colonic transit via a central corticotropin- releasing factor ( CRF), the precise mechanism still remains unclear. We tested the hypothesis that restraint stress and central CRF stimulate colonic motility and transit via a vagal pathway and 5- HT3 receptors of the proximal colon in rats. Cr-51 was injected via the catheter positioned in the proximal colon to measure colonic transit. The rats were subjected to a restraint stress for 90 min or received intracisternal injection of CRF. Ninety minutes after the administration of Cr-51, the entire colon was removed, and the geometric center ( GC) was calculated. Four force transducers were sutured on the proximal, mid, and distal colon to record colonic motility. Restraint stress accelerated colonic transit ( GC of 6.7 +/- 0.4, n = 6) compared with nonrestraint controls ( GC of 5.1 +/- 0.2, n = 6). Intracisternal injection of CRF ( 1.0 mu g) also accelerated colonic transit ( GC of 7.0 +/- 0.2, n = 6) compared with saline- injected group ( GC of 4.6 +/- 0.5, n = 6). Restraint stressinduced acceleration of colonic transit was reduced by perivagal capsaicin treatment. Intracisternal injection of CRF antagonists ( 10 mu g astressin) abolished restraint stress- induced acceleration of colonic transit. Stimulated colonic transit and motility induced by restraint stress and CRF were significantly reduced by the intraluminal administration of 5- HT3 antagonist ondansetron ( 5 x 10(-6) M; 1 ml) into the proximal colon. Restraint stress and intracisternal injection of CRF significantly increased the luminal content of 5-HT of the proximal colon. It is suggested that restraint stress stimulates colonic motility via central CRF and peripheral 5- HT3 receptors in conscious rats.