Chronic administration of morphine and naltrexone up-regulate[3H][D-Ala2,D-leu5]enkephalin binding sites by different mechanisms.
Previous studies have demonstrated that chronic administration of morphine up-regulated the lower affinity binding site for [3H][D-ala2,D-leu5]enkephalin, without producing a detectable alteration in the higher affinity binding site for [3H][D-ala2,D-leu5]enkephalin (Rothman et al., Eur. J. Pharmac. 124: 113-119, 1986). The experiments reported in this paper tested the hypothesis that chronic administration of morphine and naltrexone up-regulated the binding sites for [3H][D-ala2,D-leu5]enkephalin by different mechanisms. Rats were given either morphine or naltrexone chronically. Chronic administration of morphine up-regulated the lower affinity site, while chronic administration of naltrexone up-regulated both the higher and lower affinity binding sites for [3H][D-ala2,D-leu5]enkephalin. Unlike the lower affinity binding site for [3H][D-ala2,D-leu5]enkephalin present in membranes prepared from rats treated with placebo pellets, the lower affinity binding sites which were up-regulated by naltrexone and morphine were partially (naltrexone) or completely (morphine) labile to preincubation for 60 min at 25 degrees C in 50 mM Tris-HCl, pH 7.4, containing 0.4 M NaCl. These data suggest that chronic administration of morphine and naltrexone up-regulate binding sites for [3H][D-ala2,D-leu5]enkephalin through different mechanisms, and that the lower affinity binding sites for [3H][D-ala2, D-leu5]enkephalin which are up-regulated by chronic administration of morphine and naltrexone might differ biochemically from the lower affinity binding sites present in membranes treated with placebo.
Danks
J A
JA
Laboratory of Preclinical Pharmacology, NIMH, St. Elizabeths Hospital, Washington, DC 20002.
Tortella
F C
FC
Long
J B
JB
Bykov
V
V
Jacobson
A E
AE
Rice
K C
KC
Holaday
J W
JW
Rothman
R B
RB
D000818:Animals; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D012965:Sodium Chloride / Q000494:pharmacology
D011957:Receptors, Opioid; D012965:Sodium Chloride; D009271:Naltrexone; D009020:Morphine