Involvement of δ₂ opioid receptors in acute dependence on morphine in mice

The effects that naltriben (NTB) and naltrindole 5'-isothiocyanate (5'- NTII) have on acute morphine dependence were investigated in mice. The degree of acute dependence was estimated by the ED₅₀ value of s.c.-administered naloxone that was required to precipitate withdrawal jumping 4 hr after s.c. injection of 100 mg/kg of morphine sulfate (MS-100). Pretreatments with NTB (10 μmol/kg, s.c., 30 min before MS-100) and 5'-NTII (10 μmol/kg, s.c., 24 hr before MS-100) increased the ED₅₀ values of naloxone compared to those of the respective saline-treated control mice. Although NTB itself (up to 10 μmol/kg, s.c.) did not precipitate jumping 4 hr after MS-100, small doses of NTB (1 and 2 μmol/kg, s.c.) administered 30 min before the challenge doses of naloxone increased substantially the ED₅₀ value of naloxone. These results suggest that δ₂ opioid receptors are involved in acute dependence on morphine in mice.