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Suppression of withdrawal jumping comparison of narcotic tolerance and dependence

, : Suppression of withdrawal jumping comparison of narcotic tolerance and dependence. Drug & Alcohol Dependence 5(6): 401-410

The median and maximal suppressive doses (SD50 and SD95) of methadone and morphine for abrupt withdrawal jumping were determined in male ICR mice (25-30 g) rendered tolerant to and physically dependent on morphine after implantation with a morphine pellet for 3 days. Three separate groups of mice were then given 1 of the following treatments for 5 successive days: SD95 methadone s.c. once daily, SD95 methadone per os (p.o.) once daily and SD95 morphine s.c. every 8 h. Respective controls received either water p.o. or saline s.c. daily. The SD95 for each narcotic suppressed withdrawal jumping equally (by 80%) each day during the 5 day administration period. At the end of that time, only the morphine group demonstrated significant analgetic tolerance to s.c. morphine and methadone (a 3-fold elevation) and detectable physical dependence as evidenced by naloxone-precipitated withdrawal jumping. Daily doses of an opiate sufficient to suppress abrupt withdrawal jumping in morphine-dependent animals may not necessarily maintain the animals' tolerance and physical dependence on morphine. The sites for the expression of acute opiate analgesia and withdrawal jumping are not those involved with the development of tolerance and physical dependence.


PMID: 7189707

DOI: 10.1016/0376-8716(80)90140-4

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