Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse

Neurogastroenterol Motil. 2006 Jun;18(6):464-71. doi: 10.1111/j.1365-2982.2006.00792.x.

Abstract

Serotonin-selective reuptake transporter (SERT) expression is decreased in animal models of intestinal inflammation and in individuals with inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS), and it is possible that resultant changes in intestinal serotonin signalling contribute to the manifestation of clinical features associated with these disorders. The objective of this investigation was to determine whether inhibition of SERT function leads to changes in gut motility and sensitivity. Mice underwent a 14-day treatment with the SERT inhibitor, paroxetine (20 mg kg(-1)), or vehicle (saline/propylene glycol). Gastrointestinal (GI) transit following charcoal gavage, colonic motility, stool frequency and visceromotor responses to colorectal distension were evaluated. In mice treated with paroxetine, stool output was decreased, upper GI transit was delayed, and colonic sensitivity to a nociceptive stimulus was attenuated. These results demonstrate that reduced SERT function (via pharmacological blockade) significantly alters GI motility and sensitivity in mice, and support the concept that altered SERT expression and function could contribute to symptoms associated with IBS and IBD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colon / drug effects
  • Colon / metabolism*
  • Electromyography
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology*
  • Inflammatory Bowel Diseases / physiopathology
  • Irritable Bowel Syndrome / physiopathology
  • Male
  • Mice
  • Pain Threshold / drug effects
  • Pain Threshold / physiology*
  • Paroxetine / pharmacology
  • Serotonin Plasma Membrane Transport Proteins / drug effects
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Serotonin Uptake Inhibitors / pharmacology

Substances

  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Paroxetine