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. 1982 Jul;320(1):50-3.
doi: 10.1007/BF00499071.

Morphine- and methadone-tolerant mice differ in cross-tolerance to other opiates. Heterogeneity in opioid mechanisms indicated

A Neil

Morphine- and methadone-tolerant mice differ in cross-tolerance to other opiates. Heterogeneity in opioid mechanisms indicated

A Neil. Naunyn Schmiedebergs Arch Pharmacol. 1982 Jul.

Abstract

Mice were rendered tolerant to morphine or 1-methadone by subcutaneous injections for 4 days. The antinociceptive activities of morphine, codeine, l-methadone and d-propoxyphene were determined in tolerant and control mice using the hot-plate test, and the respective ED50's were calculated by the up-and-down procedure of Dixon. An asymmetry in cross-tolerance patterns was found: While morphine-pretreated mice were tolerant to morphine only (with a dose-ratio tolerant: control of 5.2), methadone-pretreated mice were tolerant to all analgesics tested, and more so to morphine 5.2; l-methadone 3.0; codeine 2.7 and d-propoxyphene 1.9). The results are discussed in terms of heterogeneity in opioid receptor mechanisms.

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