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

First Author  Zhu Y Year  1999
Journal  Neuron Volume  24
Issue  1 Pages  243-52
PubMed ID  10677041 Mgi Jnum  J:57886
Mgi Id  MGI:1345915 Doi  10.1016/s0896-6273(00)80836-3
Citation  Zhu Y, et al. (1999) Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice. Neuron 24(1):243-52
abstractText  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.
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