Differential tolerance to morphine's immunomodulatory effects following continuous administration.

Rats were continuously infused with either morphine or saline via an osmotic minipump for 20 consecutive days. Effects on immune status were assessed on the twentieth day of the chronic administration period following a bolus injection of morphine administered 1 h prior to sacrifice. The morphine injection suppressed measures of splenic natural killer (NK) cell activity, mitogen-stimulated T-cell proliferation, and gamma-interferon (IFN) production in rats that received saline via the minipump. In rats that received chronic morphine via the minipump, the morphine injection also suppressed mitogen-stimulated splenocyte proliferation and gamma-IFN production but did not suppress NK cell activity. These data indicate that chronic morphine administration via osmotic minipumps leads to differential tolerance to the immunomodulatory effects of morphine. These findings support previous results indicating differential tolerance development within the immune system following chronic morphine administration via the drinking water.