Opioid receptor upregulation and supersensitivity in mice: effect of morphine sensitivity.
Mice of the Swiss-Webster strain obtained from two suppliers (Taconic, Charles River) were found to differ in their sensitivity to morphine. Mice from Taconic were approximately two-fold more sensitive to the analgesic and lethal effects of morphine compared to the Charles River mice. In a third strain, C3H/HEN, morphine was found to be more than 2.5 times more potent in producing analgesia than in the Charles River mice. Binding studies showed that the Taconic mice and C3H/HEN mice had approximately 40% and 60%, respectively, more specific [3H]naloxone binding sites in brain than did the less sensitive Charles River mice. When treated with chronic naltrexone for 8 days the analgesic potency of morphine was increased by approximately 90% for both Swiss-Webster mice and by 20% for the C3H/HENs. [3H]Naloxone binding was increased by 45-50% in the Swiss-Webster strains, but by only 33% in C3H/HEN mice. These data indicate that receptor upregulation is directly related to increases in morphine potency. Further, these findings suggest that initial sensitivity to morphine can determine the degree of functional supersensitivity and relative receptor upregulation produced by chronic opioid antagonist treatment.
Yoburn
B C
BC
Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, St. John's University, Jamaica, NY 11439.
Kreuscher
S P
SP
Inturrisi
C E
CE
Sierra
V
V
D000698:Analgesia; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000378:metabolism / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism
D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine