Caffeine interferes with morphine-induced hyperactivity but not analgesia

In C57BL/6 mice caffeine antagonized morphine-induced hyperactivity. This effect was most evident when caffeine was used in doses that slightly increased locomotor activity. Given at the same dose caffeine did not affect morphine-induced analgesia. Two possibilities of explanation of this effect are discussed: action of caffeine on dopaminergic mechanisms responsible for morphine-induced running fit through its effect on cyclic AMP level, and a direct action of caffeine on delta opiate receptors involved in the stimulatory effect of morphine.