Substance P N-terminal fragment SP(1-7) attenuates chronic morphine tolerance and affects dynorphin B and nociceptin in rats |
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Authors: | Qin ZhouAnna Carlsson Mathias HallbergFred Nyberg |
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Affiliation: | Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, P.O. 591, S-751 24 Uppsala, Sweden |
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Abstract: | The N-terminal substance P fragment SP1-7 is known to modulate hyperalgesia and opioid withdrawal in animal models. This study examined the effects of intraperitoneal (i.p.) injections of SP1-7 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 (10 mg/kg) twice daily for 7 days. SP1-7 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 SP1-7 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 SP1-7 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 SP1-7 on opioid tolerance. |
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Keywords: | Dynorphin B (DYN B) Morphine Nociceptin/orphanin FQ (N/OFQ) Opioid tolerance Rat brain Substance P (SP) SP1-7 |
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