Chronic naltrexone differentially affects supraspinal delta-opioid receptor-mediated antinociception.
The effects of chronic treatment with naltrexone, an opioid receptor antagonist, on delta1- and delta2-opioid receptor agonist-induced antinociception and ligand binding were investigated in mice. Antinociception by intracerebroventricular (i.c.v.) [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II, agonists selective for delta1- and delta2-opioid receptors, respectively, was blocked following subcutaneous (s.c.) implantation of a naltrexone pellet (7.5 mg) for 7 days. Removal of the naltrexone pellet was followed 24 h later by a decrease of 7.5-fold in the ED50 value of [D-Ala2]deltorphin II, but not that of DPDPE. In a whole brain homogenate the binding of [3H][D-Ala2]deltorphin II was increased twice as much as that of [3H]DPDPE. Chronic naltrexone treatment also produced an 8.6-fold decrease in the ED50 value of i.c.v. administered morphine. The increase in morphine potency was reversed to a control (placebo-treated mice) value by the selective delta2-opioid receptor antagonist, naltriben (25 pmol, i.c.v.). Thus, chronic naltrexone selectively increases delta2-opioid receptor-mediated antinociception, supporting the existence of delta opioid receptor subtypes with distinct adaptive characteristics. The data also indicate that delta2-opioid receptors are critically involved in the expression of morphine supersensitivity.
Kest
B
B
Department of Pharmacology, LC-524, Cornell University Medical College, New York, NY 10021, USA.
Lee
C E
CE
Jenab
S
S
Kao
B
B
Inturrisi
C E
CE
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C060209:deltorphin II, Ala(2)-; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-