MORPHINE-INDUCED INCREASES OF EXTRACELLULAR HISTAMINE LEVELS IN THE PERIAQUEDUCTAL GRAY INVIVO - A MICRODIALYSIS STUDY

The effect of morphine on extracellular histamine levels in two regions of the rat midbrain was studied in vivo by microdialysis. Morphine (5.6 and 12.8 mg/kg, s.c.) significantly and dose-dependently increased extracellular histamine levels in the periaqueductal grey, while no significant effect was observed in the reticular formation. In addition, no significant effect of sequential saline injections was observed on extracellular histamine levels in the periaqueductal grey. Since morphine has no effect on histamine catabolism, these results suggest that morphine increases histamine release in the rat PAG, a site where morphine and histamine are known to have analgesic action. Taken with earlier studies showing the ability of H2 antagonists to block morphine analgesia, these results support the hypothesis that histamine and H2 receptors are important in mediating morphine analgesia in the rat periaqueductal grey. The cellular origin of the extracellular histamine, and the mechanism of this morphine effect remain to be determined.