Precipitation of abstinence like syndrome in morphine dependent mice by pargyline

E. L. Way, E. T. Iwamoto, S. Khanna, I. K. Ho, F. Shen, H. H. Loh

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In mice rendered morphine dependent by pellet implantation for 3 days, the administration of pargyline 6 hr after pellet removal intensified narcotic abstinence behavior, particularly the narcotic withdrawal jumping response. Pargyline, 75 mg/kg i.p., caused a 6 to 9 fold increase in the incidence of jumping in mice withdrawing from morphine 6 hr after removal of the pellet, whereas this effect was not observed: 1) 1 hr after the injection of pargyline or 2) in animals still implanted with the morphine pellet. The median effective dose (ED50) of pargyline required to elicit withdrawal jumping in mice implanted with morphine decreased with increasing physical dependence. The ED50 for 72 hr was about one sixth that after 24 hr of implantation. Additionally, pargyline potentiated naloxone precipitated withdrawal jumping as evidenced by a reduction of the naloxone ED50 by approx. one half. Administration of other monoamine oxidase inhibitors such as pheniprazine, iproniazid or tranylcypromine failed to alter the incidence of jumping in dependent mice undergoing abrupt morphine withdrawal. Furthermore, dopamine receptor stimulation by amphetamine, pheniprazine or amantadine antagonized the pargyline induced jumping response. These data suggest that the increased incidence of withdrawal jumping observed after pargyline in morphine dependent mice is not related to monoamine oxidase inhibition but rather to a possible pargyline induced decrease in dopaminergic activity.

Original languageEnglish (US)
Pages (from-to)400-407
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - 1976


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