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.
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.
Zhou
Qin
Q
Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, S-751 24 Uppsala, Sweden.
Carlsson
Anna
A
Botros
Milad
M
Fransson
Rebecca
R
Sandström
Anja
A
Gordh
Torsten
T
Hallberg
Mathias
M
Nyberg
Fred
F
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000737:chemistry* / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D014150:Antipsychotic Agents; D010446:Peptide Fragments; D013373:Substance P; D009270:Naloxone; C036877:substance P (1-7); C012134:SK&F 10047; D010620:Phenazocine