Genetic dissociation of opiate tolerance and physical dependence in δ-opioid receptor-1 and preproenkephalin knock-out mice Journal Article
| Authors: | Nitsche, J. F.; Schuller, A. G. P.; King, M. A.; Zengh, M.; Pasternak, G. W.; Pintar, J. E. |
| Article Title: | Genetic dissociation of opiate tolerance and physical dependence in δ-opioid receptor-1 and preproenkephalin knock-out mice |
| Abstract: | Previous experiments have shown that mice lacking a functional δ-opioid receptor (DOR-1) gene do not develop analgesic tolerance to morphine. Here we report that mice lacking a functional gene for the endogenous ligand preproenkephalin (ppENK) show a similar tolerance deficit. In addition, we found that the DOR-1 and ppENK knock-outs as well as the NMDA receptor-deficient 129S6 inbred mouse strain, which also lacks tolerance, exhibit antagonist-induced opioid withdrawal. These data demonstrate that although signaling pathways involving ppENK, DOR, and NMDA receptor are necessary for the expression of morphine tolerance, other pathways independent of these factors can mediate physical dependence. Moreover, these studies illustrate that morphine tolerance can be genetically dissociated from physical dependence, and thus provide a genetic framework to assess more precisely the contribution of various cellular and molecular changes that accompany morphine administration to these processes. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; gene mutation; promoter region; nonhuman; molecular genetics; animal cell; mouse; animals; mice; mice, knockout; animal tissue; gene targeting; gene expression; opiate; animal experiment; animal model; protein; withdrawal syndrome; in situ hybridization; immunocytochemistry; drug dependence; morphine; analgesics, opioid; drug tolerance; mu opiate receptor; knockout mouse; nociception; tolerance; opiate addiction; protein precursors; n methyl dextro aspartic acid receptor; inbred strain; sigma 1 opiate receptor; receptors, opioid, delta; nmda receptor; dependence; n methyl dextro aspartic acid; priority journal; article; μ-opioid receptor; substance withdrawal syndrome; δ-opioid receptor, preproenkephalin; preproenkephalin; protein dor 1; protein ppenk; enkephalins; morphine dependence; n-methylaspartate |
| Journal Title: | The Journal of Neuroscience |
| Volume: | 22 |
| Issue: | 24 |
| ISSN: | 0270-6474 |
| Publisher: | Society for Neuroscience |
| Date Published: | 2002-12-15 |
| Start Page: | 10906 |
| End Page: | 10913 |
| Language: | English |
| PUBMED: | 12486185 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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