Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice.
Gene targeting was used to delete exon 2 of mouse DOR-1, which encodes the delta opioid receptor. Essentially all 3H-[D-Pen2,D-Pen5]enkephalin (3H-DPDPE) and 3H-[D-Ala2,D-Glu4]deltorphin (3H-deltorphin-2) binding is absent from mutant mice, demonstrating that DOR-1 encodes both delta1 and delta2 receptor subtypes. Homozygous mutant mice display markedly reduced spinal delta analgesia, but peptide delta agonists retain supraspinal analgesic potency that is only partially antagonized by naltrindole. Retained DPDPE analgesia is also demonstrated upon formalin testing, while the nonpeptide delta agonist BW373U69 exhibits enhanced activity in DOR-1 mutant mice. Together, these findings suggest the existence of a second delta-like analgesic system. Finally, DOR-1 mutant mice do not develop analgesic tolerance to morphine, genetically demonstrating a central role for DOR-1 in this process.
Zhu
Y
Y
Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854, USA.
King
M A
MA
Schuller
A G
AG
Nitsche
J F
JF
Reidl
M
M
Elde
R P
RP
Unterwald
E
E
Pasternak
G W
GW
Pintar
J E
JE
D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D004361:Drug Tolerance; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000008:administration & dosage / Q000378:metabolism; D005091:Exons; D017353:Gene Deletion; D018390:Gene Targeting; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000235:genetics* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects; D014316:Tritium
D000701:Analgesics, Opioid; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D014316:Tritium; C059567:deltorphin; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-