Effects of befiradol on fentanyl-induced respiratory depression in adult rats. (A–B) Representative continuous whole body plethysmographic recordings from two adult rats. A 20-min infusion of fentanyl (60 μg/kg, iv) caused a significant depression of respiratory frequency (f_R) and tidal volume (V_T). (A) Saline or (B) befiradol (0.2 mg/kg, iv, bolus) was injected approximately 6 min after administration of fentanyl. Respiratory variables and oxygen saturation were measured before fentanyl, and 5 to 20 min after administration of fentanyl. Nociceptive testing via tail clamping was performed starting approximately 11 min after fentanyl administration. (C–F) Dose-dependence data showing the relative respiratory frequency (f_R, C), tidal volume (V_T, D), minute ventilation (V_E, E), and oxygen saturation (Sao₂, F) after injection of vehicle or increasing doses of befiradol approximately 6 min after fentanyl infusion. Respiratory variables (f_R, V_T, and V_E,) are presented as % relative to control (i.e., prefentanyl administration). Each animal tested only once with vehicle or one dose of befiradol. *Significant difference, compared with vehicle control group; #compared between two doses of befiradol-treatment groups; and using two way repeated measures ANOVA (Holm–Sidak methods).