Suppression by dynorphin A-(1–13) of the expression of opiate withdrawal and tolerance in mice

Dynorphin A-(1–13) has been shown to suppress the expression of opiate withdrawal and tolerance dose dependently in morphine-dependent mice when administered i.v. The ED50 of naloxone to precipitate withdrawal jumping was increased by 1.5- and 7-fold when morphine-dependent mice were pretreated with 2.5 and 5.0 μmol/kg of dynorphin A-(1–13), respectively. When dynorphin A-(1–13) (5.0 μmol/kg, i.v.) was administered after the precipitation of withdrawal with naloxone, the ED50 of naloxone was still increased by over 2-fold. Also, the expression of tolerance which was estimated by noting the antinociceptive ED50 of morphine, was inhibited by over 70% with a dynorphin A-(1–13) dose of 2.5 μ mol/kg and completely suppressed by pretreatment with 5.0 μmol/kg of dynorphin A-(1–13) i.v. The mechanism by which dynorphin A-(1–13) produces these effects when given i.v. remains to be elucidated.