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The effect of ethanol on loperamide‐induced tolerance (653.15)
Author(s) -
Khan Fayez,
Stevens David,
Scoggins Krista,
Akbarali Hamid,
Dewey William
Publication year - 2014
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.28.1_supplement.653.15
Subject(s) - loperamide , morphine , ileum , gastrointestinal transit , pharmacology , ethanol , opioid , drug tolerance , medicine , agonist , meal , chemistry , receptor , diarrhea , biochemistry
We have reported that the mechanism for the production of morphine tolerance differs in the brain and ileum. In more recent studies we have shown that ethanol reversed morphine antinociceptive tolerance in a dose dependent manner. Therefore we investigated the ability of ethanol to reverse the tolerance produced by chronic exposure to Loperamide, a peripherally selective μ‐opioid receptor agonist that inhibits gastrointestinal motility. Gastrointestinal transit was measured by intragastric gavage of a charcoal meal. In vehicle treated mice, the leading edge of charcoal after 30 min transits 74 ± 6 % (n=6) of the length of the ileum. When Loperamide (0.1‐10 mg/kg) was administered subcutaneously 15 minutes before charcoal meal gavage, it significantly and dose‐dependently inhibited gastrointestinal transit. Loperamide (30 mg/kg) given acutely inhibited intestinal transit by 75%. When this dose was administered subcutaneously twice daily for two days and again at 15 minutes before oral injection of the charcoal meal the inhibitory effect on gastrointestinal transit was reduced to 46% (n=6) inhibition; suggesting that tolerance to loperamide occurred. When Loperamide (30 mg/kg) was chronically administered subcutaneous twice daily for two days and on the third day, ethanol (1g/kg) was injected intraperitoneally 30 minutes before a loperamide (30 mg/kg) challenge dose, the inhibition was 47% (n=6) indicating that ethanol did not reverse the tolerance produced by loperamide. These data suggest that ethanol reverses opioid tolerance to central efffects but not to their effects on the ileum. Grant Funding Source : Supported by NIH DA024009 and ASPET SURF Award (FK)