Effects of serotonin transporter inhibition on gastrointestinal motility and colonic sensitivity in the mouse.
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.
Coates
M D
MD
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Johnson
A C
AC
Greenwood-Van Meerveld
B
B
Mawe
G M
GM
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004576:Electromyography; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000503:physiopathology; D008297:Male; D051379:Mice; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D017374:Paroxetine / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors