Retention of supraspinal delta-like analgesia and loss of morphine tolerance in δ opioid receptor knockout mice

Yanxin Zhu, Michael A. King, Alwin G.P. Schuller, Joshua F. Nitsche, Maureen Reidl, Robert P. Elde, Ellen Unterwald, Gavril W. Pasternak, John E. Pintar

Research output: Contribution to journalArticlepeer-review

350 Scopus citations

Abstract

Gene targeting was used to delete exon 2 of mouse DOR-1, which encodes the δ 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 δ1 and δ2 receptor subtypes. Homozygous mutant mice display markedly reduced spinal δ analgesia, but peptide δ agonists retain supraspinal analgesic potency that is only partially antagonized by naltrindole. Retained DPDPE analgesia is also demonstrated upon formalin testing, while the nonpeptide 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.

Original languageEnglish (US)
Pages (from-to)243-252
Number of pages10
JournalNeuron
Volume24
Issue number1
DOIs
StatePublished - Sep 1999

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Retention of supraspinal delta-like analgesia and loss of morphine tolerance in δ opioid receptor knockout mice'. Together they form a unique fingerprint.

Cite this