Potentiation of opioid analgesia in dopamine2 receptor knock-out mice: Evidence for a tonically active anti-opioid system Journal Article
| Authors: | King, M. A.; Bradshaw, S.; Chang, A. H.; Pintar, J. E.; Pasternak, G. W. |
| Article Title: | Potentiation of opioid analgesia in dopamine2 receptor knock-out mice: Evidence for a tonically active anti-opioid system |
| Abstract: | Dopamine systems are intimately involved with opioid actions. Pharmacological studies suggest an important modulatory effect of dopamine and its receptors on opioid analgesia. We have now examined these interactions in a knock-out model in which the dopamine2 (D2) receptor has been disrupted. Loss of D2 receptors enhances, in a dose-dependent manner, the analgesic actions of the μ analgesic morphine, the κ1 agonist U50,488H and the κ3 analgesic naloxone benzoylhydrazone. The responses to the δ opioid analgesic [D-Pen2, D-Pen5]enkephalin were unaffected in the knock-out animals. Loss of D2 receptors also potentiated spinal orphanin FQ/nociceptin analgesia. Antisense studies using a probe targeting the D2 receptor revealed results similar to those observed in the knock-out model. The modulatory actions of D2 receptors were independent of σ receptor systems because the σ agonist (+)-pentazocine lowered opioid analgesia in all mice, including the D2 knock-out group. Thus, dopamine D2 receptors represent an additional, significant modulatory system that inhibits analgesic responses to μ and κ opioids. |
| Keywords: | nonhuman; mouse; animals; mice; mice, knockout; opiate; animal experiment; animal model; dose-response relationship, drug; heterozygote; drug synergism; morphine; analgesics, opioid; pain measurement; analgesia; receptors, opioid, mu; dopamine; concentration response; knockout mouse; nociception; analgesic agent; naloxone; enkephalin[2,5 dextro penicillamine]; oligonucleotides, antisense; opioid peptides; dopamine receptor; pentazocine; receptors, opioid, delta; receptors, sigma; analgesic; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; naloxone benzoylhydrazone; neurotransmission; knock-out; antisense; dopamine 2 receptor; dopamine antagonists; receptors, dopamine d2; male; priority journal; article; receptors, opioid, kappa; anti-opioid; d2 receptor; 3,4-dichloro-n-methyl-n-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-isomer; enkephalin, d-penicillamine (2,5)-; sulpiride |
| Journal Title: | The Journal of Neuroscience |
| Volume: | 21 |
| Issue: | 19 |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Date Published: | 2001-10-01 |
| Start Page: | 7788 |
| End Page: | 7792 |
| Language: | English |
| PUBMED: | 11567069 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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