Substance P-(1-7), a substance P metabolite, inhibits withdrawal jumping in morphine-dependent mice

Julie S. Kreeger, Alice A. Larson

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30 Scopus citations


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 μg 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.

Original languageEnglish (US)
Pages (from-to)111-115
Number of pages5
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - Jul 6 1993

Bibliographical note

Funding Information:
This work was supported by United States Public Health Service Grants NIDA04190, 04090 and 00124 to A.A.L. and NIDAO7234 to J.S.K.

Copyright 2014 Elsevier B.V., All rights reserved.


  • (Intrathecal)
  • Morphine withdrawal
  • Substance P
  • Substance P N-terminus

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