Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Female B6C3F1 mice were rendered tolerant-dependent on morphine by a combination of injections and pellet implantation. Mice were injected with morphine sulfate (20 mg/kg, s.c.) twice a day on day 1. On day 2, they were implanted s.c. with a 75 mg morphine pellet for 3 days. On day 5, the pellets were either left intact (tolerant) or removed 8 h prior (abstinent) to carrying out the immune function tests. A high degree of tolerance to the analgesic and hypothermic effect of morphine developed as a result of this procedure. Similarly, physical dependence also developed as evidenced by the signs of the abrupt and naltrexone-precipitated abstinence syndrome. Implantation with morphine pellets resulted in a profound, statistically significant reduction in spleen and thymus weight and cellularities, with the greatest degree of reduction noted in abstinent animals. Morphine tolerance was associated with suppressed B-cell proliferation following in vitro stimulation, as well as interleukin-2 (IL-2) and interleukin-4 production by T-cells. NK cell activity was significantly reduced in morphine-tolerant, but not in morphine-abstinent, mice following a 24 h incubation in the presence or absence of IL-2. In comparison, the in vitro induction of cytotoxic T-cells was significantly depressed in morphine-abstinent, but not morphine-tolerant, animals. Exposure to morphine apparently had limited effect on macrophage function as assessed by production of tumor necrosis factor. These studies demonstrate a differential effect on immune effector and regulatory mechanisms in morphine tolerance and abstinence processes.
 ...
PMID:Effects of morphine tolerance and abstinence on cellular immune function. 803 70

The immunomodulatory effects of dihydroetorphine were systematically investigated in subchronically treated mice. In a dose-dependent fashion, dihydroetorphine (total doses at 444.5, 889 and 1778 microg/kg) lowered the increase of body weight, decreased the weight of the spleen and thymus, weakened the delayed-type hypersensitivity, reduced the generation of antibody-forming cells, inhibited splenic lymphocyte proliferation induced by concanavalin A and lipopolysaccharide, suppressed the production of interleukin-2 in the supernatant of splenocytes induced by concanavalin A, and depleted the ratio of CD4+ and CD8+ subpopulations. Moreover, the physical dependence on dihydroetorphine was also evaluated to confirm that the immunosuppression was concomitant with the addiction to the drug. These results demonstrate that subchronic treatment with dihydroetorphine dose dependently suppresses both humoral and cell-mediated immune function, and that the immunosuppressive effects of dihydroetorphine are much more potent than those of morphine.
 ...
PMID:Immunosuppressive effects of dihydroetorphine, a potent narcotic analgesic, in dihydroetorphine-dependent mice. 1008 8