Effect of pargyline on morphine tolerance and physical dependence development in mice.
The effects of single and repeated pargyline administration on morphine antinociception in both naive and morphine-tolerant mice and on naloxone-precipitated withdrawal in morphine tolerant-dependent animals were investigated. Adult, male Swiss-Webster mice were rendered tolerant to and dependent on morphine by the s.c. pellet implantion technique. Morphine analgesia, as assessed by the tail-flick antinociceptive test, was potentiated in tolerant animals by acute adminstration of pargyline but antagonized by repeated pargyline administration; pargyline produced similar effects in non-tolerant mice and to the same relative degree. Repeated pargyline treatment during morphine pellet implantation enhanced the withdrawal jumping response precipitated by naloxone in dependent mice. Pargyline also, after a single injection, exacerbated jumping in mice undergoing abrupt withdrawal. Neither acute nor chronic pargyline administration altered the brain distribution of injected morphine in non-tolerant mice. It was concluded that pargyline may modify acute morphine actions and withdrawal without materially altering the process(es) involved in the development of tolerance and physical dependence.
D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D004361:Drug Tolerance; D006801:Humans; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D009020:Morphine / Q000032:analysis / Q000494:pharmacology*; D009021:Morphine Dependence / Q000209:etiology*; D009270:Naloxone / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced
D009270:Naloxone; D009020:Morphine; D010293:Pargyline; D008995:Monoamine Oxidase