The C-terminal amidated analogue of the Substance P (SP) fragment SP (1-7) attenuates the expression of naloxone- precipitated withdrawal in morphine dependent rats
2009 (English)In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 30, no 12, 2418-2422 p.Article in journal (Refereed) Published
We previously demonstrated that intracerebroventricular (i.c.v.) administration of the substance P (SP) aminoterminal fragment SP(1-7) attenuates the expression of morphine withdrawal in the male rat. In this study we have used a synthetic analogue of this peptide, i.e. the SP(1-7) amide showing higher binding potency than the native heptapeptide, in a similar experimental set-up. Thus, Wistar male rats were made tolerant to morphine by daily injections of the opiate during 8 days. Following peptide administration (i.c.v.) and a subsequent naloxone challenge a variety of physical syndromes of withdrawal were recorded. We observed that the SP(1-7) amide potently and dose-dependently reduced several signs of reaction to morphine withdrawal. Interestingly, the effect of the peptide amide was significantly attenuated by the addition of the sigma agonist (+)-SKF-10047. We conclude that the SP(1-7) amide mimics the effect of the native SP fragment and that the mechanisms for its action involve a sigma receptor site.
Place, publisher, year, edition, pages
2009. Vol. 30, no 12, 2418-2422 p.
Morphine, Opiate, Substance P (SP), SP1-7 amide, Rat, Withdrawal, Sigma receptor
IdentifiersURN: urn:nbn:se:uu:diva-97824DOI: 10.1016/j.peptides.2009.08.009ISI: 000272903900044PubMedID: 19686790OAI: oai:DiVA.org:uu-97824DiVA: diva2:172907