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The effect of pretreatment with a δ2-opioid receptor antisense oligodeoxynucleotide on the recovery from acute antinociceptive tolerance to δ2-opioid receptor agonist in the mouse spinal cord
- Source :
- British Journal of Pharmacology. 120:587-592
- Publication Year :
- 1997
- Publisher :
- Wiley, 1997.
-
Abstract
- 1. An intrathecal (i.t.) injection of a selective delta 2-opioid receptor agonist, [D-Ala2]deltorphin II, produced an acute antinociceptive tolerance to the antinociceptive effect of a subsequent i.t. challenge of [D-Ala2]deltorphin II. This acute tolerance lasted 3 to 9 h and completely subsided by 12 h. The experiments were designed to examine the effect of pretreatment with an antisense oligodeoxynucleotide to delta 2-opioid receptor mRNA (delta-AS oligo) on the recovery from tolerance to [D-Ala2]deltorphin II-induced antinociception in male ICR mice. 2. Pretreatment with delta-AS oligo (1.63 to 163 pmol, i.t.), but not mismatched oligo (MM oligo) (163 pmol), prevented the recovery from acute tolerance to [D-Ala2]deltorphin II-induced antinociception in a dose-dependent manner. However, treatment with delta-AS oligo (163 pmol) did not prevent the recovery from tolerance to either the mu-opioid receptor agonist [D-Ala2,NMePhe4,Gly(ol)5]enkephalin (DAMGO) or the kappa-opioid receptor agonist U50,488H, indicating subtype specificity in the mechanism by which delta-AS oligo inhibits recovery from delta 2-opioid tolerance. 3. Treatment with [D-Ala2]deltorphin II (i.t.) significantly reduced the binding of [tyrosyl-3,5-(3)H(N)]-Tyr-D-Ser-Gly-Phe-Leu-Thr ([3H]-DSLET), a delta 2-opioid receptor agonist ligand, in the spinal cord 3 h after treatment, but binding returned to control levels by 24 h after treatment. However, [3H]-DSLET binding in the spinal cord remained significantly reduced at 24 h if delta-AS oligo (163 pmol) was coadministered with [D-Ala2]deltorphin II (6.4 nmol). 4. Based on these findings, it is concluded that a single stimulation of spinal cord delta 2-opioid receptors by intrathecally-administered [D-Ala2]deltorphin II induces a long-lasting desensitization of delta 2-opioid receptors to [D-Ala2]deltorphin II. Recovery from delta 2-opioid receptor-mediated antinociceptive tolerance apparently depends on replenishment by newly synthesized delta 2-opioid receptor protein rather than immediate reversal of delta 2-opioid receptors.
- Subjects :
- Male
Agonist
medicine.medical_specialty
Pyrrolidines
Enkephalin
medicine.drug_class
Stimulation
Pharmacology
Mice
chemistry.chemical_compound
Drug tolerance
Opioid receptor
Receptors, Opioid, delta
Internal medicine
medicine
Animals
RNA, Antisense
Receptor
Injections, Spinal
Pain Measurement
Mice, Inbred ICR
Dose-Response Relationship, Drug
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
Drug Tolerance
Enkephalins
Enkephalin, Ala(2)-MePhe(4)-Gly(5)
Analgesics, Opioid
DAMGO
Endocrinology
chemistry
Papers
Deltorphin
Oligopeptides
Enkephalin, Leucine
Subjects
Details
- ISSN :
- 00071188
- Volume :
- 120
- Database :
- OpenAIRE
- Journal :
- British Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....5af5a6272b899c7550dbf45215f3a4a4