Naloxone-precipitated (0.5 mg/kg, i.p.) withdrawal jumps and global scores following 7 days of chronic infusion with (A) morphine (12, 24, 48 mg/kg/day, s.c.; two-way ANOVA analysis for genotype effect for jumps (P=0.0180) and global score (P=0.004), WT vs KO: *P<0.05, ***P<0.001, Bonferroni post-hoc analysis, n=8-11 WT, 7-10 KO), (B) methadone (48, 60, 72 mg/kg, s.c., n=8-10 WT, 8-10 KO), (C) fentanyl (0.8, 1.6, 3.2 mg/kg, s.c., n=7-11 WT, 6-10 KO) or, (D) oxycodone (12.5, 25, 75 mg/kg, s.c., n=5-6 WT, 5 KO). Immediately following naloxone administration, withdrawal signs were observed and scored over a 30 min period. Data are presented as the mean ± S.E.M. For methadone, fentanyl, and oxycodone, two-way ANOVA analysis revealed no differences for genotype effect for both jumps (P>0.05) and global score (P>0.05).