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• W2018482116 abstract "Mice treated chronically with opioid antagonists have increased receptor density in brain and are supersensitive to the pharmacodynamic action of morphine. In the present study mice were implanted subcutaneously with naltrexone or placebo pellets for 8 days. During implantation mice received daily injections of morphine (100 or 250 mg/kg) or saline. Morphine analgesia was completely blocked in mice that were implanted with naltrexone at the low dose of morphine; while some analgesic action was observed at the higher dose. Mice implanted with placebo were analgesic following the daily morphine treatment. At the end of 8 days the pellets were removed and 24 h later some mice were tested for morphine analgesia while others were examined in binding studies. Naltrexone treatment increased [3H]naloxone,3H[d-Ala2-d-Leu5]enkephalin (DADLE) and3H[d-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) binding compared to controls and increased the analgesic potency of morphine. Daily treatment with morphine did not alter brain opioid binding or naltrexone-induced receptor upregulation. Mice injected daily with morphine were significantly less sensitive to morphine (tolerant) than their respective saline control group for both the placebo and the naltrexone-treated groups. However, naltrexone-treated mice were more sensitive to morphine than placebo controls regardless of whether they were injected daily with morphine or not. These results indicate that if naltrexone-induced opioid receptor upregulation occurs in the presence of repeated agonist administration, the new binding sites mediate tolerance via desensitization to morphine." @default.
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• W2018482116 date "1990-10-01" @default.
• W2018482116 modified "2023-10-16" @default.
• W2018482116 title "Simultaneous development of opioid tolerance and opioid antagonist-induced receptor upregulation" @default.
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• W2018482116 doi "https://doi.org/10.1016/0006-8993(90)90821-r" @default.
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