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Journal of Pharmacology And Experimental Therapeutics, Vol. 140, Issue 2, 149-154, 1963
Copyright © 1963 by American Society for Pharmacology and Experimental Therapeutics

A SIMPLE METHOD FOR PRODUCING TOLERANCE TO DIHYDROMORPHINONE IN MICE

Louis Shuster 1, Ruth V. Hannam 1, and William E. Boyle Jr. 1

1 Department of Pharmacology, Tufts University School of Medicine, Boston, Massachusetts

Mice became tolerant within a few days to the analgesic and exciting effects of narcotics as a result of drinking dilute evaporated milk containing dihydromorphinone HCl (Dilaudid). Tolerant mice could be maintained in good physical condition for 1 month or more while drinking between 50 and 70 mg per kg of dihydro-morphinone HCl daily.

When tolerant mice were withdrawn they lost as much as 15% of their body weight over-night, indicating that physical dependence was established.

The extent of tolerance increased with increasing daily intake of dihydromorphinone and with the length of time, up to about 7 days, that animals were maintained on one given dose.

Mice made tolerant by drinking dihydromorphinone showed decreased excitability. This was manifested by decreased spontaneous activity and a decreased response to the exciting effects of morphine, meperidine, codeine, cocaine, and, to a lesser extent, d-amphetamine. There was tolerance to the analgesic effects of morphine, meperidine and cocaine.

The assay, by means of a photoelectric counter, of motor activity following a test dose of narcotic is a sensitive and convenient method for measuring narcotic tolerance in mice.

Submitted on July 17, 1962
Accepted on January 28, 1963






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Copyright © 1963 by the American Society for Pharmacology and Experimental Therapeutics.