Abstract
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When tolerant mice were withdrawn they lost as much as 15% of their body weight over-night, indicating that physical dependence was established.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.
Footnotes
- Received July 17, 1962.
- Accepted January 28, 1963.
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