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.