Substance P-(1-7), a substance P metabolite, inhibits withdrawal jumping in morphine-dependent mice.
Substance P has been previously shown to inhibit the intensity of the morphine abstinence syndrome in mice. In view of the rapid degradation of substance P after its release from nerve terminals, we hypothesized that this inhibition is mediated by the N-terminus of substance P and its metabolites rather than via the C-terminus interacting with neurokinin receptors. Intrathecal injection of substance P-(1-7) (1 nmol) 30 min prior to naloxone challenge, in mice that had received 25 micrograms of morphine sulfate intrathecally once daily for three days, caused a dose-related attenuation of withdrawal jumping. In contrast, administration of the substance P-(1-7) antagonist, [D-Pro2,D-Phe7]substance P-(1-7), 15 min prior to naloxone increased withdrawal jumping behaviors. Equimolar doses of morphine and naloxone at 30 min had no effect. From these data, it appears that substance P N-terminal metabolites modulate withdrawal behaviors in morphine-dependent mice.
Kreeger
J S
JS
Department of Veterinary PathoBiology, University of Minnesota, St. Paul 55108.
Larson
A A
AA
D000818:Animals; D004347:Drug Interactions; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology / Q000633:toxicity*; D009021:Morphine Dependence; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D013373:Substance P / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D010446:Peptide Fragments; D013373:Substance P; D009270:Naloxone; C036877:substance P (1-7); D009020:Morphine