Interactions between imipramine and morphine on motility in rats: possible relation to antidepressant effects?

The aim of the present study was to evaluate whether morphine and the more modern antidepressant drug imipramine have common effects on behavior after both acute and chronic administration, and, in particular, to establish whether they act synergistically. In rats, morphine (15 mg/kg i.p.) produced a pronounced hypokinesia, followed by locomotor activation and stereotyped behavior. After repeated administration (eight times), tolerance to the hypokinesia developed, whereas locomotor activation and stereotypies occurred earlier and were more pronounced. Subacute pretreatment with imipramine (twice daily 10 mg/kg i.p. for eight days) enhanced and prolonged hypokinesia and delayed the manifestation of stereotypies and locomotor activation. In contrast, chronic treatment with imipramine (for 29 days) no longer inhibited morphine-induced stereotypies and locomotor activation, but seemed to enhance them when they were tested in rats repeatedly treated with morphine. When the same rats were tested with morphine (15 mg/kg) seven days after withdrawal of morphine and imipramine, morphine produced increased stereotypies and a slight enhancement of locomotion. The experimental conditions used excluded the possibility that conditioning phenomena might explain the enhancement of (probably dopamine-mediated) behavior. Furthermore, the results demonstrated that 1) acute administration of morphine and subacute administration of imipramine may act in a synergistic way, and 2) repeated administration of morphine and chronic treatment with imipramine also act synergistically, although contrary to the acute actions of both drugs. These interactions might be of therapeutic or toxicological relevance.