CENTRAL CCK-8S RECEPTORS TRIGGER THE SIGMA LIGAND-INDUCED AND 5-HT(1A) AGONISTS-INDUCED ACCELERATION OF POSTPRANDIAL COLONIC TRANSIT IN RATS

The effects of igmesine (JO 1784) and 5-HT1A agonists (8-OH-DPAT, busp irone) on post-prandial colonic transit were evaluated in conscious ra ts chronically fitted with an intracolonic catheter inserted into the proximal colon. Colonic transit time was evaluated by intracolonic adm inistration of a radiolabelled marker ([Cr-51]sodium chromate) and col lection of the faeces, per hour, on a conveyor belt. In control studie s, the colonic mean retention time was 7.8 +/- 1.9 h and faecal dry ma tter was 50.1 +/- 8.4%. Intraperitoneal treatment with igmesine (1 mg kg-1) reduced the colonic mean retention time by 61.1%, but was inacti ve at 0.1 and 0.25 mg kg-1. Buspirone (10 mg kg-1 IP) and 8-OH-DPAT(0. 1 mg kg-1) injected i.p. reduced the mean retention time. The stimulat ory effect of buspirone on colonic transit was dose-related (0.1-10 mg kg-1). Neither igmesine, buspirone nor 8-OH-DPAT affected the faecal dry matter. Intracerebroventricular (i.c.v.) injection of igmesine (0. 025 and 0.1 mg kg-1) also reduced the post-prandial mean retention tim e by 41.6 and 41.7%, respectively, without any effect on faecal dry ma tter. In contrast, intracerebroventricular injection of 8-OH-DPAT or b uspirone had no effect on colonic mean retention time. Subcutaneous in jection with BMY 14802 (1 mg kg-1) completely prevented the igmesine- (0.1 mg kg-1 i.c.v.) induced reduction of mean retention time; further more, spiroxatrine (0.5 mg kg-1 s.c.) blocked both buspirone- (10 mg k g-1 i.p.) and 8-OH-DPAT- (0.1 mg kg-1 i.p.) induced stimulation of pos t-prandial colonic transit. Intracerebroventricular but not i.p. injec tion of devazepide (10 mug kg-1) inhibited the stimulating effect of i gmesine, 8-OH-DPAT or buspirone on colonic transit, while L365,260 was inactive. In rats igmesine and 5-HT1A agonists stimulate colonic tran sit by a mechanism involving the central release of CCK-8s and/or the activation of supraspinal CCKergic pathways and these effects are medi ated through CCK(A)-type receptors.