Morphine analgesia: 2-way cross tolerance between systemic and intracerebral (periaqueductal gray) administrations.

Two-way analgesic cross tolerance was obtained between systematic and intracerebral morphine injections in the periaqueductal gray. When rats were pretreated with intraperitoneal morphine and tested with intracerebral morphine in the periaqueductal gray, a dose-dependent reduction in analgesia as a function of morphine pretreatment level was obtained. Conversely, when rats were pretreated with intracerebral morphine, significant reductions in analgesia were obtained. These results are further confirmation that the periaqueductal gray matter is an important site for morphine analgesia.