title: Substance P N-terminal fragment SP(1-7) attenuates chronic morphine tolerance and affects dynorphin B and nociceptin in rats.
abstract: The N-terminal substance P fragment SP(1-7) is known to modulate hyperalgesia and opioid withdrawal in animal models. This study examined the effects of intraperitoneal (i.p.) injections of SP(1-7) on chronic morphine tolerance and on the levels of dynorphin B (DYN B) and nociceptin/orphanin FQ (N/OFQ) in various brain areas of male Sprague-Dawley rats. Morphine tolerance was induced by subcutaneous injections of the opioid (10mg/kg) twice daily for 7 days. SP(1-7) injected i.p. (185 nmol/kg) 30 min prior to morphine reduced the development of morphine tolerance. Immunoreactive (ir) DYN B and N/OFQ peptide levels were measured in several areas of the central nervous system. Levels of ir DYN B in rats treated with SP(1-7) and morphine were decreased in the nucleus accumbens, substantia nigra and ventral tegmental area and increased in the frontal cortex. The ir N/OFQ levels were increased in the periaqueductal gray and decreased in the nucleus accumbens. Since the concentration profiles of the two peptides were altered by SP(1-7) in the areas that are implicated in the modulation of opioid tolerance and analgesia, it is suggested that DYN B and N/OFQ systems may be involved in the effects of SP(1-7) on opioid tolerance.
authors.affiliation: Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, P.O. 591, S-751 24 Uppsala, Sweden.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Anna
authors.initials: A
authors.lastname: Carlsson
authors.forename: Mathias
authors.initials: M
authors.lastname: Hallberg
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D004399:Dynorphins / Q000494:pharmacology*; D004723:Endorphins / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010147:Pain Measurement; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology*; D000097629:Nociceptin
chemical_list: D000701:Analgesics, Opioid; D004399:Dynorphins; D004723:Endorphins; D009020:Morphine; D018847:Opioid Peptides; D010446:Peptide Fragments; D013373:Substance P; D000097629:Nociceptin; C036877:substance P (1-7); C036200:rimorphin