Tolerance development to morphine-induced alterations of immune status.

A variety of in vitro immune measures were examined in groups of Lewis rats that chronically consumed either tap water or a 0.2, 0.4, or 0.6 mg/ml morphine drinking solution. Rats received a subcutaneous injection of either saline or 15 mg/kg morphine sulfate 1 h before sacrifice. In the drinking groups, the acute morphine injection significantly suppressed splenic natural killer (NK) cell activity, mitogen-stimulated splenic T- and B-cell proliferation and gamma-interferon (gamma-IFN) production. A single, acute injection of morphine did not suppress NK cell activity in rats that drank the two highest concentrations of morphine, whereas it did suppress the mitogen-stimulated splenic T- and B-cell proliferation and gamma-IFN production. These results suggest that rats that drank morphine for 20 days developed tolerance to morphine's suppressive effect on NK cell activity but not to other measures of immune status. Morphine drinking rats also developed tolerance to morphine's antinociceptive effects and revealed signs of physical dependence when the morphine solution was withdrawn or when naltrexone was administered.