The Effects of Duloxetine on Spontaneous and Oxytocin-Induced Contractions of the Rat Uterine Smooth Muscle

Duloxetine (DX) is used in the treatment of depression, anxiety and diabetic neuropathic pain. However, It also has side effects such as muscle pain, stiffness and cramps. Therefore, this study aimed to investigate the possible effects of duloxetine on contractile parameters of rat uterine smooth muscle in vitro. Sixteen adult female rats were randomly assigned into control (n=8) and DX (n=8) groups. Following ketamine-xylazine anesthesia, rats were sacrificed by cervical dislocation, and uterine tissues were isolated and transferred into Krebs-Henseleit solution. Longitudinal uterine strips (20×3 mm) were mounted in an isolated organ bath (IOB) system. After the equilibration period, DX was administered cumulatively at concentrations of 1.5, 15, 30, and 60 μM, while the control group received equivalent volumes of vehicle. Contractions were also induced with 10⁻⁷ M oxytocin (OXT). Vehicle applications did not produce significant differences between groups overall (p>0.05); however, the highest volume (V4) significantly reduced contraction frequency compared to baseline (p=0.0282). DX (1.5–60 μM) caused a dose-dependent and highly significant inhibition in contraction force, AUC and contraction frequency during spontaneous uterine contractions (p<0.0001). This inhibitory effect was especially prominent at 60 μM, where contraction frequency decreased to 28.45±8.63%. Similarly, DX significantly and dose-dependently inhibited all parameters of OXT-induced contractions (p<0.0001). Partial recovery was observed after the washout period, and no significant differences were detected between groups indicated by the same letter (p>0.05). DX causes a dose-dependent reduction and inhibition in both spontaneous and OXT-induced uterine smooth muscle contractions.