title: The antinociceptive effects of intravenous tianeptine in colorectal distension-induced visceral pain in rats: the role of 5-HT₃ receptors.
abstract: Tianeptine is an unusual tricyclic antidepressant drug. In this study, we aimed to investigate the antinociceptive effect of tianeptine on visceral pain in rats and to determine whether possible antinociceptive effect of tianeptine is mediated by serotonergic (5-HT(2,3)) and noradrenergic (α(1,2)) receptor subtypes. Male Sprague Dawley rats (250-300 g) were supplied with a venous catheter, for drug administrations, and enameled nichrome electrodes, for electromyography, at external oblique musculature. Colorectal distension (CRD) was employed as the noxious visceral stimulus and the visceromotor response (VMR) to CRD was quantified electromyographically before and 5, 15, 30, 60, 90 and 120 min after tianeptine administration. Antagonists were administered 10 min before tianeptine for their ability to change tianeptine antinociception. Intravenous administration of tianeptine (2.5-20 mg/kg) produced a dose-dependent reduction in VMR. Administration of 5-HT(3) receptor antagonist ondansetron (0.5, 1 and 2 mg/kg), but not 5-HT(2) receptor antagonist ketanserine (0.5, 1 and 2 mg/kg), reduced the antinociceptive effect of tianeptine (10mg/kg). In addition, administration of α(1)-adrenoceptor antagonist prazosin (1 mg/kg) or α(2)-adrenoceptor antagonist yohimbine (1 mg/kg) did not cause any significant effect on the tianeptine-induced antinociception. Our data indicate that intravenous tianeptine exerts a pronounced antinociception against CRD-induced visceral pain in rats, and suggests that the antinociceptive effect of tianeptine appears to be mediated in part by 5-HT(3) receptors, but does not involve 5-HT(2) receptors or α-adrenoceptors.
authors.affiliation: Ondokuz Mayıs University, School of Medicine, Department of Pharmacology, Samsun, Turkey. ssbilge@omu.edu.tr
authors.forename: S Sırrı
authors.initials: SS
authors.lastname: Bilge
authors.forename: Ayhan
authors.initials: A
authors.lastname: Bozkurt
authors.forename: Fatih
authors.initials: F
authors.lastname: Ilkaya
authors.forename: Engin
authors.initials: E
authors.lastname: Ciftcioğlu
authors.forename: Yüksel
authors.initials: Y
authors.lastname: Kesim
authors.forename: Tayfun I
authors.initials: TI
authors.lastname: Uzbay
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000378:metabolism*; D013841:Thiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D059265:Visceral Pain / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D000929:Antidepressive Agents, Tricyclic; D011942:Receptors, Adrenergic, alpha; D044348:Receptors, Serotonin, 5-HT2; D044406:Receptors, Serotonin, 5-HT3; D013841:Thiazepines; C050504:tianeptine