Preadministration of varenicline or ABT 594 alleviated fentanyl-induced respiratory depression. (A and B) Representative whole-body plethysmographic recordings from three adult rats. (A) Seven minutes after saline (neck subcutaneously), administration of fentanyl (36 μg/kg over 10 min, iv) caused a marked depression of respiratory frequency (f_R) and minute ventilation (). (B) Preadministration of varenicline (1 mg/kg, subcutaneously) approximately 7 min before fentanyl reduced the fentanyl-induced decrease of f_R, and . (C) Preadministration of ABT 594 (30 µg/kg, subcutaneously) approximately 7 min before fentanyl reduced the fentanyl-induced decrease of f_R, and . (D–F) Population data (mean and SD) showing f_R (D), (E) relative to control before fentanyl administration, and oxygen saturation (F) with preadministration of varenicline (1 mg/kg, subcutaneously), ABT 594 (30 µg/kg, subcutaneously), or saline approximately 7 min before fentanyl. *P < 0.05, **P < 0.01, ***P < 0.001, statistically significant difference compared with saline group, using two-way repeated-measures ANOVA (Holm–Sidak method). n = 8 animals each data point.