σ1 receptor modulation of opioid analgesia in the mouse Journal Article
| Authors: | Mei, J.; Pasternak, G. W. |
| Article Title: | σ1 receptor modulation of opioid analgesia in the mouse |
| 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 κ3 opioid 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. |
| Keywords: | controlled study; genetics; dose response; drug potentiation; nonhuman; mouse; animal; animals; mice; animal tissue; haloperidol; animal experiment; down-regulation; drug effect; mice, inbred balb c; central nervous system; physiology; drug receptor binding; drug synergism; narcotic analgesic agent; bagg albino mouse; nucleotide sequence; binding site; down regulation; mouse strain; analgesics, opioid; pain measurement; drug sensitivity; analgesia; pain assessment; morphine sulfate; mu opiate receptor; injections, spinal; oligodeoxyribonucleotides, antisense; naloxone; enkephalin[2,5 dextro penicillamine]; delta opiate receptor; pentazocine; sigma 1 opiate receptor; receptors, sigma; receptor down regulation; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; nalbuphine; kappa opiate receptor; antisense oligodeoxynucleotide; narcotic antagonist; narcotic antagonists; halothane; male; priority journal; article; nalorphine; sigma opiate receptor; sigma-1 receptor; intraspinal drug administration |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 300 |
| Issue: | 3 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 2002-03-01 |
| Start Page: | 1070 |
| End Page: | 1074 |
| Language: | English |
| DOI: | 10.1124/jpet.300.3.1070 |
| PUBMED: | 11861817 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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