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Opiate Receptor Knockout Mice Define μ Receptor Roles in Endogenous Nociceptive Responses and Morphine-Induced Analgesia

Ichiro Sora, Nobuyuki Takahashi, Masahiko Funada, Hiroshi Ujike, Randal S. Revay, David M. Donovan, Lucinda L. Miner and George R. Uhl
Proceedings of the National Academy of Sciences of the United States of America
Vol. 94, No. 4 (Feb. 18, 1997), pp. 1544-1549
Stable URL: http://www.jstor.org/stable/41368
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Opiate Receptor Knockout Mice Define μ  Receptor Roles in Endogenous Nociceptive Responses and Morphine-Induced Analgesia
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Abstract

Morphine produces analgesia at opiate receptors expressed in nociceptive circuits. μ , δ , and κ opiate receptor subtypes are expressed in circuits that can modulate nociception and receive inputs from endogenous opioid neuropeptide ligands. The roles played by each receptor subtype in nociceptive processing in drug-free and morphine-treated states have not been clear, however. We produced homologous, recombinant μ , opiate receptor, heterozygous and homozygous knockout animals that displayed ≈ 54% and 0% of wild-type levels of μ receptor expression, respectively. These mice expressed κ receptors and δ receptors at near wild-type levels. Untreated knockout mice displayed shorter latencies on tail flick and hot plate tests for spinal and supraspinal nociceptive responses than wild-type mice. These findings support a significant role for endogenous opioid-peptide interactions with μ opiate receptors in normal nociceptive processing. Morphine failed to significantly reduce nociceptive responses in hot plate or tail flick tests of homozygous μ receptor knockout mice, and heterozygote mice displayed right and downward shifts in morphine analgesia dose-effect relationships. These results implicate endogenous opioid-peptide actions at μ opiate receptors in several tests of nociceptive responsiveness and support μ receptor mediation of morphine-induced analgesia in tests of spinal and supraspinal analgesia.

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