Antagonism of heroin and morphine self-administration in rats by the morphine-6β-glucuronide antagonist 3-O-methylnaltrexone Journal Article
| Authors: | Walker, J. R.; King, M.; Izzo, E.; Koob, G. F.; Pasternak, G. W. |
| Article Title: | Antagonism of heroin and morphine self-administration in rats by the morphine-6β-glucuronide antagonist 3-O-methylnaltrexone |
| Abstract: | In mice, 3-O-methylnaltrexone blocks the analgesic actions of morphine-6β-glucuronide and heroin at doses which are inactive against morphine. We found a similar selectivity in rats. 3-O-Methylnaltrexone antagonized the analgesic actions of 6-acetylmorphine in Sprague-Dawley rats and heroin in Wistar rats at doses that were inactive against morphine. Inclusion of a fixed dose of 3-O-methylnaltrexone significantly shifted the analgesic dose-response curves for 6-acetylmorphine and heroin without altering the morphine dose-response curves. In a self-administration model, 3-O-methylnaltrexone treatment significantly increased both heroin and morphine intake during the first hour, suggestive of an antagonist effect. This effect at doses of 3-O-methylnaltrexone which were inactive against morphine analgesia implied a role for the morphine-6β-glucuronide opioid receptor in the reinforcing properties of heroin and morphine. Copyright (C) 1999 Elsevier Science B.V. |
| Keywords: | controlled study; unclassified drug; dose response; nonhuman; animals; animal experiment; dose-response relationship, drug; drug antagonism; rat; rats; rats, sprague-dawley; morphine; drug abuse; pain measurement; rats, wistar; injections, subcutaneous; tail flick test; intravenous drug administration; naloxone; opiate receptor; diamorphine; morphine 6 acetate; morphine 6 glucuronide; naltrexone; analgesic activity; heroin; opiate addiction; addiction; opiate antagonist; morphine-6-glucuronide; quaternary ammonium compounds; narcotic antagonists; subcutaneous drug administration; morphine derivatives; narcotics; reinforcement; self administration; drug self administration; self-administration; male; priority journal; article; 3 o methylnaltrexone; conditioning, operant |
| Journal Title: | European Journal of Pharmacology |
| Volume: | 383 |
| Issue: | 2 |
| ISSN: | 0014-2999 |
| Publisher: | Elsevier B.V. |
| Date Published: | 1999-10-27 |
| Start Page: | 115 |
| End Page: | 119 |
| Language: | English |
| DOI: | 10.1016/s0014-2999(99)00633-0 |
| PUBMED: | 10585524 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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