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

The effects of naltrexone on tolerance/dependence, as well as alterations in cellular immune function induced by morphine administration, were determined. Mice were rendered tolerant to and physically dependent on morphine by subcutaneous implantation of pellets containing 75 mg of morphine. Implantation of naltrexone pellets (10 mg) blocked the development of tolerance to the analgesic action of morphine, as well as the development of physical dependence. Morphine suppressed lymphoid organ weights and cellularities, and this suppression was blocked by naltrexone. B-Cell proliferation was suppressed in morphine-tolerant but not in morphine-abstinent mice, and this suppression was exacerbated by naltrexone. Morphine tolerance and abstinence were associated with suppression of IL-2 production, which was completely blocked by naltrexone. NK cell activity was not significantly affected by either morphine or naltrexone exposure. The results suggest that the effects of morphine on the immune system are at least partially mediated through opioid receptors.
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PMID:Effects of naltrexone on morphine-induced tolerance and physical dependence and changes in cellular immune function in mice. 749 98

Opiates are potent analgesic and addictive compounds. They also act on immune responses, and morphine, the prototypic opiate, has been repeatedly described as an immunosuppressive drug. Pharmacological studies have suggested that the inhibitory action of opiates on immunity is mediated by multiple opioid receptor sites but molecular evidence has remained elusive. Recently, three genes encoding mu- (MOR), delta-, and kappa-opioid receptors have been cloned. To investigate whether the mu-opioid receptor is functionally implicated in morphine immunosuppression in vivo, we have examined immune responses of mice with a genetic disruption of the MOR gene. In the absence of drug, there was no difference between wild-type and mutant mice with regard to a large number of immunological endpoints, suggesting that the lack of MOR-encoded protein has little consequence on immune status. Chronic morphine administration induced lymphoid organ atrophy, diminished the ratio of CD4(+)CD8(+) cells in the thymus and strongly reduced natural killer activity in wild-type mice. None of these effects was observed in MOR-deficient mice after morphine treatment. This demonstrates that the MOR gene product represents a major molecular target for morphine action on the immune system. Because our previous studies of MOR-deficient mice have shown that this receptor protein is also responsible for morphine analgesia, reward, and physical dependence, the present results imply that MOR-targeted therapeutic drugs that are developed for the treatment of pain or opiate addiction may concomitantly influence immune responses.
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PMID:Abolition of morphine-immunosuppression in mice lacking the mu-opioid receptor gene. 960 Sep 64