Figure 4.

Nicotine induction of brain CYP2D increased the first 30 min of codeine-induced analgesia, an effect that was blocked by inhibiting brain CYP2D. Compared with vehicle pretreatment, 7 days of nicotine pretreatment or propranolol pretreatment alone resulted in significantly higher and lower, respectively, %MPE (a) and analgesic AUC_0–30 min (b) after codeine administration. Compared with vehicle pretreatment, co-pretreatment of nicotine and propranolol together resulted in a significantly different %MPE and AUC_0–30 min than nicotine or propranolol pretreatment alone and no change in %MPE or AUC_0–30 min from vehicle pretreatment (n=12/group). Error bars indicate SEM. A within-animal study design was used; *p<0.05, **p<0.01, ***p<0.001, compared with vehicle, and ^#p<0.05, ^##p<0.01, compared with the combination pretreatment, using repeated-measures ANOVA with a Bonferroni post hoc test.