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Use of a μ-antisense oligodeoxynucleotide as a μ opioid receptor noncompetitive antagonist in vivo

  • Physiology and Behavior
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Abstract

We examined whether μ-antisense (AS) oligodeoxynucleotide (oligo) treatment can be used in a manner similar to the μ-selective irreversible antagonist β-funaltrexamine (β-FNA) for in vivo pharmacology. Rats were injected intracerebroventricularly (icv) with a μ-AS or a missense (MS) oligo on days 1, 3, 5, 7, and 9 and were tested for the antinociceptive effect of sc injection of morphine on days 2, 4, 6, 8, and 10 in the cold water tail-flick (CWT) test. In another set of experiments, rats were also tested for the antinociceptive action of morphine twenty-four hours after icv injection of β-FNA. Both β-FNA and μ-AS produced rightward shifts in the dose-effect curves of morphine. In addition, pretreatment with 2.5 μg or more of β-FNA or the μ-AS oligo for 5–9 days (but not for 1–3 days) reduced the maximal analgesic effect of morphine. The approximate fraction of functional receptor remaining for morphine was determined with the method of Furchgott to be 49.5% following 2.5 μg of β-FNA; that after 5 days of the μ-AS oligo treatment was 50.8%. The results suggest that the μ-AS oligo can be used in the same manner as highly selective, irreversible μ opioid receptor ligands. Thus, properly designed AS oligos against receptors are of particular benefit when irreversible antagonists are not available. AS oligos represent a new class of selective and powerful pharmacological antagonists.

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Authors and Affiliations

  1. Fels Institute for Molecular Biology and Cancer Center, Temple University School of Medicine, 19140, Philadelphia, PA

    J. Kim de Riel

  2. Department of Pharmacology, Temple University School of Medicine, 3420 N. Broad Street, 19140, Philadelphia, PA

    Xiao-Hong Chen M.D., Lee-Yuan Liu-Chen, Ronald J. Tallarida, Ellen B. Geller & Martin W. Adler

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  1. Xiao-Hong Chen M.D.
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  2. Lee-Yuan Liu-Chen
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  3. Ronald J. Tallarida
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  5. J. Kim de Riel
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Special issue dedicated to Dr. Eric J. Simon.

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Chen, XH., Liu-Chen, LY., Tallarida, R.J. et al. Use of a μ-antisense oligodeoxynucleotide as a μ opioid receptor noncompetitive antagonist in vivo. Neurochem Res 21, 1363–1368 (1996). https://doi.org/10.1007/BF02532377

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