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 mumol/kg of dynorphin A-(1-13), respectively. When dynorphin A-(1-13) (5.0 mumol/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 mumol/kg and completely suppressed by pretreatment with 5.0 mumol/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.
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis 55455.
A E
AE
Takemori
H H
HH
Loh
N M
NM
Lee
D000818:Animals; D004361:Drug Tolerance; D004399:Dynorphins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000009:adverse effects; D009270:Naloxone / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000188:drug therapy; D010446:Peptide Fragments / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D010446:Peptide Fragments; D009270:Naloxone; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine