Disruption of Serotonin Signaling Results in Loss of Coordinated Tone Development and Subsequent Inhibition of Peristalsis in Guinea Pig Distal Colon

This project was designed to examine the effects of the selective serotonin reuptake inhibitor, Fluoxetine, on colonic motility using the isolated guinea pig distal colon. The Gastrointestinal Motility Monitor system (“GIMM”, Catamount Research and Development Inc., St. Albans, VT) was used to analyze peristaltic motility during fecal pellet propulsion, as well as to conduct spatiotemporal analysis of motility patterns. Peristaltic motility in colonic segments was significantly slowed by Fluoxetine at concentrations of 20, 30 and 40 μM (p<0.05 vs. vehicle). Indeed, in colonic segments treated with 40 μM Fluoxetine, peristaltic motility was completely abolished (at least 1 of 3 trials with no peristaltic motility) in 4 out of 5 experimental preparations. This striking disruption in peristaltic motility by Fluoxetine was associated with a pronounced change in spatiotemporal motility patterns. In the presence of 40 μM Fluoxetine, average colonic diameter during the motility trial was substantially increased relative to pre‐treatment diameter (36.6 ± 21.5 % increase from baseline diameter, n=5). In vehicle‐treated colonic segments, average diameter remained relatively unchanged from pre‐treatment levels (0.5 ± 3.5 % change from baseline diameter, n=11). These findings suggest that serotonin signaling in the wall of the gut is required for normal peristaltic propulsive motility, and that disruption of serotonin signaling using Fluoxetine results in a loss of coordinated tone in the wall of the gut. Understanding the exact role of serotonin in normal gut motility is essential to gaining insights into novel therapeutic strategies for treating bowel dysfunction. Support or Funding Information This study was supported by Catamount Research and Development