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.
Bibliographical noteFunding Information:
Correspondence to: A.E. T;~k~mori.Dcp;trtmrnt ol’ Pharmecolopy. 3-24Y Millard Iinll. University of Minnesota. 435 IIrlaw;lrc St. S.E.. Minneapolis. MN 5.5455. USA. Tel. I 012-03-324X. fax I hl?-h25-X40X. This investigation was supported hy U.S. Public IlCillIh Scrvicc grants from the Nution;! Institute on Drug Abuse. Studies in lhis rcpurt were curried out in ;uzcord;mrr with the IIeclar;ilion 01 Ijclsinki ;md/or with the Guide for the (‘;Irc :IIKIU SC ol’ L;lhoralorS Animals ;Is ;~loptcd ;IIMIp ramulgotcd by the N;ltioual Institutes of Ilculth.
- Dynorphin A-(1-13)
- Opiate tolerance
- Opiate withdrawal