Abstract
The opioid μ receptor antagonist β-funaltrexamine (β-FNA) blocked the development of physical dependence in rats when infused simultaneously with morphine for 6 days. In addition, β-FNA given s.c. 24 h prior to the initiation and on day 3 of a 6 day period of morphine infusion in rats reduced the development of physical dependence in a dose-dependent manner. In morphine-dependent rhesus monkeys, β-FNA precipitated a prompt and long-lasting withdrawal, which was not reversed within by 30 h by subsequent injections of morphine. In contrast, naloxone-induced withdrawal lasted approximately 90 min. These results provide further evidence that β-FNA is a long-acting antagonist of the opioid μ receptor, and that this receptor has a major role in the development of morphine-induced physical dependence.
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