Drugs used in this study were: morphine hydrochloride (Merck & Co., Inc., Rahway, NJ); morphine-6-O-sulfate (sodium salt, prepared in our laboratory as described previously13 (link)); the δ-OR selective antagonist naltrindole hydrochloride (NLD; Tocris Biosciences, Minneapolis, MN); the κ-OR selective antagonist norbinaltorphimine hydrochloride (nor-BNI; a generous gift from Dr. Philip Portoghese, University of Minnesota, Minneapolis, MN): and non-selective opioid antagonist naltrexone hydrochloride (NTX; Sigma Aldrich, St. Louis, MO). All drugs were prepared in physiological saline immediately prior to use. The volume of intraperitoneal (i.p.) injections for all animals was 2 mL/kg of rat body weight. The control group of animals received an equivalent volume of the vehicle only. Treatment of animals with OR antagonists was conducted as described previously. Drugs were injected i.p. 30 min (NTX 2 mg/kg) 14 (link),20 (link) (NLD 1 mg/kg) 14 (link),21 (link) or 18 hr (nor-BNI 5 mg/kg) 14 (link),22 (link) prior the time of peak antinociceptive effect of M6S or morphine.