Figure 3.

Nicotine-mediated induction of brain CYP2D increased codeine analgesia and had no effect on morphine-induced analgesia. Rats were administered nicotine (1 mg/kg; s.c.) or saline vehicle (s.c.) once daily for 7 days as outlined (a). As measured on the final day of nicotine pretreatment, plasma nicotine levels peaked within the first 30 min and were undetectable by 8 h, the time of codeine or morphine administration (n=16; b). Mean plasma nicotine levels averaged over 8 h was approximately 70 ng/ml and over 24 h was approximately 25 ng/ml. Compared with vehicle pretreatment, nicotine pretreatment (darker bar) resulted in significantly higher %MPE (c) and analgesic AUC_0–30 min (d) after codeine administration (n=20/group). Seven days of nicotine pretreatment (darker bars) did not result in a difference in analgesic AUC_0–30 min or AUC_{30–60 min} (e) after a morphine injection (n=16/group; hatched bars). Error bars indicate SEM. A within-animal study design was used; for analgesia–time curves, **p<0.01 using repeated-measures ANOVA with Bonferroni post hoc. For AUCs, *p<0.05 using paired t-tests.