Selective loss of δ opioid analgesia and binding by antisense oligodeoxynucleotides to a δ opioid receptor

Kelly M. Standifer, Chih Cheng Chien, Claes Wahlested, George P. Brown, Gavril W. Pasternak

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Abstract

Antisense oligodeoxynucleotides (18-20 bases) to a cloned δ opioid receptor (DOR-1) lower δ binding in NG108-15 cells by 40%-50%. Changing 4 bases to generate a mismatch antisense oligodeoxynucleotide or mixing the corresponding sense and antisense oligodeoxynucleotides prior to treatment of the cells eliminates the inhibition of binding, confirming the specificity of the response. In vivo, an antisense oligodeoxynucleotide to DOR-1 given intrathecally lowers δ, but not μ or κ1 spinal analgesia. The mismatch antisense oligodeoxynucleotide is inactive. δ analgesic sensitivity gradually returns by 5 days after the last antisense treatment, indicating the lack of irreversible damage or toxicity. These studies demonstrate that DOR-1 mediates δ analgesia at the level of the spinal cord and confirm at the molecular level traditional pharmacological studies implying distinct receptor mechanisms for δ, μ, and κ1 analgesia. The use of antisense approaches may prove valuable in understanding the receptors mediating opioid pharmacology.

Original languageEnglish (US)
Pages (from-to)805-810
Number of pages6
JournalNeuron
Volume12
Issue number4
DOIs
StatePublished - Apr 1994
Externally publishedYes

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ASJC Scopus subject areas

  • Neuroscience(all)

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