Inhibition by Z-Pro-D-Leu of development of tolerance to and physical dependence on morphine in mice.

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Abstract
The peptide Z-Pro-D-Leu, injected daily in mice receiving morphine chronically, prevented development of physical dependence as measured by changes in body temperature and body weight due either to abrupt or to naloxone-induced withdrawal. Administration of Z-Pro-D-Leu was effective in blocking the development of tolerance to the analgesic and the hypothermic effects of subsequent challenge doses of morphine. The peptide treatment did not alter the acute effects of a challenge dose of morphine on either analgesia or body temperature. No effects on memory were noted, as evaluated in a 1-trial passive avoidance task. Clinical implications of the use of Z-Pro-D-Leu were discussed.