Coadministration of varenicline alleviated fentanyl-induced respiratory depression. (A and B) Representative whole-body plethysmographic recordings from two adult rats. Fentanyl was administered at a dose of 90 μg/kg over 45 min (iv infusion), and saline or varenicline was administered (1 mg/kg, iv, 2 min) at the beginning of fentanyl administration. (A) Coadministered with saline, fentanyl caused a marked depression of respiratory frequency (f_R) and minute ventilation (). (B) Coadministration with varenicline reduced the fentanyl-induced decrease of f_R, and . (C–E) Population data showing f_R (C), (D) relative to control before fentanyl administration (mean and SD), and oxygen saturation (E, median and interquartile ranges). *P < 0.05, **P < 0.01, statistically significant difference compared with saline group, using two-way repeated-measures ANOVA (Holm–Sidak method) for C and D, or Mann–Whitney rank sum test for E. n = 9 animals each data point.