Effects of methadone and/or heroin on extracellular NAc DA. (a) The dose effects of methadone (0, 5, or 8 mg/kg, i.p.) on NAc DA. (b) Percent changes (%) in NAc DA after methadone and subsequent heroin administration (over premethadone baseline). (c) Renormalized percent changes (%) in NAc DA after heroin administration (over the new preheroin baseline). (d) Methadone at 5 mg/kg shifted heroin dose effects on extracellular DA downward and to the right. *p<0.05, **p<0.01, ***p<0.001, compared with baseline before methadone or heroin administration. #p<0.05, ##p<0.01, ###p<0.001, compared with the vehicle + heroin treatment group.