Abstract
Intrathecal pretreatment of mice with an antisense oligodeoxynucleotide directed against the kappa-1 receptor significantly reduced the antinociceptive effects of the kappa receptor agonist U50,488 as well as delta 9-THC, the major psychoactive ingredient found in cannabis. A mismatched oligodeoxynucleotide which contained four switched bases did not block the antinociception produced by U50,488 or delta 9-THC. Furthermore, kappa-1 antisense did not alter the antinociceptive effects of either the mu receptor-selective opioid DAMGO, or the delta receptor-selective opioid DPDPE. By using kappa-1 antisense, we were able to demonstrate that an interaction occurs between the cannabinoids and opioids in the spinal cord.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Analgesics / antagonists & inhibitors*
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Animals
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Base Sequence
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Dronabinol / antagonists & inhibitors*
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Enkephalin, D-Penicillamine (2,5)-
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Enkephalins / pharmacology
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Male
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Mice
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Mice, Inbred ICR
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Molecular Sequence Data
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Oligonucleotides, Antisense / pharmacology*
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Pain / physiopathology*
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Psychotropic Drugs / antagonists & inhibitors*
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Pyrrolidines / antagonists & inhibitors
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Receptors, Opioid, kappa / drug effects*
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Spinal Cord / drug effects*
Substances
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Analgesics
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Enkephalins
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Oligonucleotides, Antisense
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Psychotropic Drugs
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Pyrrolidines
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Receptors, Opioid, kappa
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Dronabinol
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Enkephalin, D-Penicillamine (2,5)-