Influence of immune stimulation and suppression on morphine physical dependence and tolerance.

The role of the immune system in the development of physical dependence and tolerance to morphine was studied in mice in which the immune response was either stimulated or suppressed. Immunization of mice against morphine increased the blood and brain levels of morphine as compared to controls. However, the development of physical dependence and tolerance was decreased. The chronic responses to morphine were also decreased by nonspecific immunosuppression (vincristine-cyclophosphamide treatment and gamma-irradiation exposure) and specific immunosuppression (antithymocyte and antilymphocyte sera treatment). Immunosuppressive treatments did not alter the rate of morphine absorption from the subcutaneous depot used to induce chronic exposure to the drug. However, the blood and brain levels of morphine were higher than control after 72 hours of morphine pellet implantation. It is apparent that manipulation of the immune system can alter the physical dependence and tolerance development to morphine.