The serotonin reuptake inhibitor citalopram does not affect colonic sensitivity or compliance in rats.
Altered serotonin signaling has been implicated in the pathophysiology of irritable bowel syndrome (IBS). Selective serotonin reuptake inhibitors (SSRI) improve IBS symptoms, although the mechanism of action remains unclear. We assessed the effects of the SSRI, citalopram, on colonic sensitivity and compliance in rats after acute and repeated administration. Colorectal distension was performed in conscious rats. Pressure-volume relationships during colorectal distension (2-20 mmHg), fitted using a power exponential model [Vol=V(max)xexp[-(kappaxRelP)(beta)], were used as a measure of colonic compliance. The visceral pain-related visceromotor response during colorectal distension (10-80 mmHg) was used to assess visceral sensitivity. Pressure-volume curves and visceromotor responses were assessed after acute citalopram (3 or 10 mg/kg, ip) or vehicle and after repeated treatment (7 and 14 days; 3 or 10 mg/kg/day). In vehicle-treated animals, pressure-volume curves were similar over time. Citalopram (acute or repeated treatment) did not affect neither the pressure-volume curves nor the visceromotor response to colorectal distension. Thus, citalopram, after acute or repeated administration, had no significant effects on colon compliance or visceral pain during colorectal distension in rats. These results agree with recent observations in humans suggesting that the therapeutic actions of citalopram in IBS are independent of any effects on colonic sensorimotor function.
Käll
Erika
E
Integrative Pharmacology--Gastrointestinal Biology, AstraZeneca R&D, SE-431 83 Mölndal, Sweden.
Lindström
Erik
E
Martinez
Vicente
V
D000779:Anesthetics, Local / Q000627:therapeutic use; D000818:Animals; D015283:Citalopram / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D003109:Colonic Diseases, Functional / Q000188:drug therapy* / Q000503:physiopathology; D003187:Compliance / Q000187:drug effects; D005260:Female; D008012:Lidocaine / Q000627:therapeutic use; D008954:Models, Biological; D017699:Pelvic Pain / Q000188:drug therapy*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
D000779:Anesthetics, Local; D015283:Citalopram; D008012:Lidocaine; D017367:Selective Serotonin Reuptake Inhibitors