Inhibition of protein phosphatases alters the expression of morphine tolerance in mice

European Journal of Pharmacology
M A Bernstein, S P Welch

Abstract

Recently our laboratory found that tolerance to morphine-induced antinociception could be completely reversed with intracerebroventricular (i.c.v.) administration of a protein kinase A inhibitor, whereas intrathecal (i.t.) administration of the inhibitor produced hyperalgesia in morphine-tolerant mice. In the experiments described here, we sought to characterize further the role of phosphorylation events in supraspinal versus spinal opioid-mediated pain pathways and how such events might be involved in the development of antinociceptive tolerance. Two phosphatase inhibitors were administered centrally to determine whether they affected morphine-induced antinociception in naive or chronically morphine-treated mice. By the i.c.v. route, okadaic acid enhanced morphine-induced antinociception in tolerant mice and produced toxicity by the i.t. route. The calcineurin inhibitor ascomycin had no effect on antinociception following acute or chronic morphine treatment. These results suggest that increased activity of protein phosphatase types 1 and/or 2A in the brain may contribute to the development of morphine tolerance.

References

Jan 1, 1985·Annual Review of Pharmacology and Toxicology·T L Yaksh, R Noueihed
Jan 1, 1984·Annual Review of Neuroscience·A I Basbaum, H L Fields
Jul 20, 1964·Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie·L S HARRIS

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Citations

Jan 20, 2007·Pharmacology, Biochemistry, and Behavior·María OcañaEsperanza Del Pozo
Jul 13, 2006·Life Sciences·Zaijie Jim Wang, Lili X Wang

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