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Research ArticleNEUROPHARMACOLOGY

ς1 Receptor Modulation of Opioid Analgesia in the Mouse

Jianfeng Mei and Gavril W. Pasternak
Journal of Pharmacology and Experimental Therapeutics March 2002, 300 (3) 1070-1074; DOI: https://doi.org/10.1124/jpet.300.3.1070
Jianfeng Mei
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Gavril W. Pasternak
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Abstract

Opioid analgesia is influenced by many factors, including the ς1 receptor system. Current studies show the importance of supraspinal mechanisms in these ς1 actions. Given supraspinally, the ς1 receptor agonist (+)pentazocine diminished systemic μ, δ, κ1, and κ3opioid analgesia in CD-1 mice. There was a trend for the κ drugs to be more sensitive to the fixed dose of (+)pentazocine, although the differences did not achieve statistical significance. In contrast to its actions supraspinally, (+)pentazocine was without effect against morphine when both were given spinally. These findings are consistent with a supraspinal site of anti-opioid action of (+)pentazocine. Down-regulating supraspinal ς1 binding sites using an antisense approach potentiated μ, δ, κ1, and κ3 analgesia in CD-1 mice. Although equally responsive to μ drugs, BALB-c mice are far less sensitive to κ analgesics than CD-1 mice. Earlier studies reported that these different responses to κ drugs between CD-1 and BALB-c were eliminated by the concurrent administration of haloperidol, a ς1 antagonist. Antisense treatment of BALB-c mice markedly enhanced the response to κ drugs, as well as morphine. This enhanced response following antisense treatment was similar to that seen with haloperidol. These observations confirm the importance of ς1 receptors as a modulatory system influencing the analgesic activity of opioid drugs.

Footnotes

  • This work was supported, in part, by research grant from the National Institute on Drug Abuse (DA06241) and a Senior Scientist Award (DA000220) from NIDA (to G.W.P.), and a core grant to Memorial Sloan-Kettering Cancer Center from the National Cancer Institute (CA008748).

  • Abbreviations:
    (±)SKF-10097
    (±)-N-allyl-normetazocine, DPDPE, [d-Pen2,d-Pen5]enkephalin
    NalBzoH
    naloxone benzoylhydrozone
    AS1
    antisense treatment
    bp
    base pair
    U50,488H
    trans-(dl)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate hydrate
    • Received October 10, 2001.
    • Accepted November 28, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 300 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 300, Issue 3
1 Mar 2002
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Research ArticleNEUROPHARMACOLOGY

ς1 Receptor Modulation of Opioid Analgesia in the Mouse

Jianfeng Mei and Gavril W. Pasternak
Journal of Pharmacology and Experimental Therapeutics March 1, 2002, 300 (3) 1070-1074; DOI: https://doi.org/10.1124/jpet.300.3.1070

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Research ArticleNEUROPHARMACOLOGY

ς1 Receptor Modulation of Opioid Analgesia in the Mouse

Jianfeng Mei and Gavril W. Pasternak
Journal of Pharmacology and Experimental Therapeutics March 1, 2002, 300 (3) 1070-1074; DOI: https://doi.org/10.1124/jpet.300.3.1070
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