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Morphine induced tolerance to mouse intestinal but not colonic transit and constipation
Author(s) -
Gabra Bichoy H,
Ross Gracious R,
Akbarali Hamid I,
Dewey William L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.712.14
Subject(s) - morphine , gastrointestinal transit , defecation , placebo , medicine , constipation , feces , laxative , pharmacology , anesthesia , biology , paleontology , alternative medicine , pathology
The objectives of the present studies were to compare the development of tolerance to antinociception, constipation, intestinal and colonic transit in the mouse. Eight‐ (morphine pellet) and 45‐ (morphine pellet plus supplemental injections) fold antinociceptive tolerance to morphine were developed by standard techniques. Defecation was measured daily as the number of fecal boli and weight of feces. In both tolerant groups defecation was significantly reduced at 24h, 48h and 72h, compared to placebo‐pelleted mice, indicating that tolerance did not develop to morphine‐induced constipation. The effects of a 10 mg/kg dose of morphine on antinociception, intestinal and colonic transit were determined 72h following pellet‐implantation. Acute morphine reduced intestinal transit of a charcoal meal administered orally by 50% in placebo‐pelleted mice but did not produce a similar reduction in animals chronically exposed to morphine indicating the development of tolerance. The time for the expulsion of a glass bead inserted 3 cm proximal to the anus was used to measure colonic transit. Acute morphine significantly reduced the bead expulsion time in both placebo‐ and morphine‐pelleted mice indicating no tolerance. These findings confirm that chronic morphine produces tolerance to antinociception and intestinal transit but not to colonic transit or defecation. Supported by DK46367, DA01647, DA020836