Pretreatment of mice with a single injection of morphine, β-endorphin, Leu-enkephalin, FK33824 or [D-Ala2-D-Leu5]enkephalin, for 3 h increased the ability of naloxone to antagonize the analgesic effects of morphine. However, dynorphin-(1-13) can only antagonize morphine. β-endorphin or Leu-enkephalin induced increased naloxone efficacy but not FK33824 or [D-Ala2-D-Leu2]enkephalin. Dynorphin itself can also increase naloxone efficacy when treated alone. However, this effect can be prevented when animals are pretreated with dynorphin and naloxone together.
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Supported in part by NIDA grant No. DA-02643. The authors thank Dr. Andrew P. Smith for his editorial assistance.