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Naltrexone‐Precipitated Opioid Withdrawal and Morphine‐Tolerance in Buprenorphine‐ or Methadone‐Treated Mice
Author(s) -
Paronis Carol
Publication year - 2015
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.29.1_supplement.614.1
Subject(s) - naltrexone , buprenorphine , methadone , opioid , morphine , pharmacology , ed50 , medicine , opioid receptor , opiate , (+) naloxone , anesthesia , receptor
Receptor internalization by mu‐opioid agonists has been negatively correlated to opioid tolerance and dependence. Buprenorphine does not promote mu‐opioid receptor phosphorylation yet previous reports suggest that it also does not produce opioid dependence in mice. Experiments sought to determine whether naltrexone‐precipitated withdrawal or antinociceptive‐tolerance in buprenorphine‐treated mice varies with time since the last injection; results were compared to mice treated daily with methadone (which promotes mu‐opioid receptor internalization). Naltrexone, 1‐10 mg/kg, did not elicit jumping at 4hr after 3 mg/kg/day buprenorphine yet at 24‐72hr after 0.3‐3.0 mg/kg buprenorphine, 0.1‐1.0 mg/kg naltrexone increased jumping. In contrast, the antinociceptive dose‐effect function of morphine (control ED50 = 4.2 mg/kg) was shifted 20‐fold to the right 4hr after 3 mg/kg/day buprenorphine, yet no tolerance was seen 24hr after buprenorphine. Naltrexone‐precipitated jumping also occurred at 4 and 24hr after 20 mg/kg/day methadone; in contrast to effects following buprenorphine, naltrexone was more potent at 4 than at 24hr after methadone injections. No tolerance to morphine was seen at either time point in mice treated with 20 mg/kg/day methadone, however the morphine dose‐effect function was shifted 3‐fold to the right following 45 mg/kg/day methadone. These results indicate that expression of opioid tolerance and dependence varies with time following either buprenorphine or methadone injection. (Supported by DA035411 and DA035857)