The antinociceptive effects of intravenous tianeptine in colorectal distension-induced visceral pain in rats: The role of 5-HT3 Receptors.
Özet
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-HT2,3) and noradrenergic (α1,2) 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-HT3 receptor antagonist ondansetron (0.5, 1 and 2 mg/kg), but not 5-HT2 receptor antagonist ketanserine
(0.5, 1 and 2 mg/kg), reduced the antinociceptive effect of tianeptine (10 mg/kg). In addition, administration
of α1-adrenoceptor antagonist prazosin (1 mg/kg) or α2-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-HT3 receptors, but does not involve
5-HT2 receptors or α-adrenoceptors.