Antinociceptive response in prenatally saline-exposed male rats after acute or the third (or second) injection of different opioids. Rats received an acute injection of morphine (10 mg/kg), methadone (5 mg/kg), or buprenorphine (1.5 mg/kg), s.c., at age 8-12 weeks. (A) The latency and the AUC of the first morphine, methadone, or buprenorphine injection. (B) The latency and the AUC of the 3rd morphine and methadone or the 2nd buprenorphine injection. (C) Rate of tolerance development to different opioids in prenatally saline-exposed rats. The rate of tolerance development showed a steeper slope in the buprenorphine-treated group than that of the morphine- or methadone-treated group. All data are expressed as mean ± S.E.M, (N = 4 in methadone and buprenorphine treatment group; N = 19 in morphine treatment group), *p < 0.05, ***p < 0.001 compared to buprenorphine group.