Differential tolerance to morphine's immunomodulatory effects following continuous administration

Rats were continuously infused with either morphine or saline via an osmoti c 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 in jection suppressed measures of splenic natural killer (NK) cell activity, m itogen-stimulated T-cell proliferation, and gamma-interferon (IFN) producti on in rats that received saline via the minipump. In rats that received chr onic morphine via the minipump, the morphine injection also suppressed mito gen-stimulated splenocyte proliferation and gamma-IFN production but did no t suppress NK cell activity. These data indicate that chronic morphine admi nistration via osmotic minipumps leads to differential tolerance to the imm unomodulatory effects of morphine. These findings support previous results indicating differential tolerance development within the immune system foll owing chronic morphine administration via the drinking water. (C) 1998 Else vier Science Ireland Ltd. All rights reserved.