EFFECTS OF PROLONGED EXPOSURE TO MORPHINE AND METHADONE ON IN-VIVO PARAMETERS OF IMMUNE FUNCTION IN RATS

In rats, two 6-week repeated dose oral toxicity studies were performed with morphine (250 and 500 mg/kg food) and methadone (200 and 400 mg/ kg food), respectively. Alterations in immune function were studied by assessing primary and secondary immune responses to sheep red blood c ells. In addition, the ability to resist challenge with infectious age nts was measured in host resistance models employing the parasite Tric hinella spiralis and the bacterium Listeria monocytogenes. The primary and secondary antibody responses to spleen red blood cells were not a ffected by treatment with either morphine or methadone. The clearance of L. monocytogenes bacteria in the spleen was not affected either. Pr olonged treatment with morphine, however, resulted in a decrease in ho st resistance to T. spiralis infection, as indicated by a 1.5-fold inc rease in numbers of muscle larvae counted in the carcass, but did not affect the T. spiralis-specific IgM, IgG and IgE antibody responses. I n contrast to morphine, the methadone-treated animals did not show a s ignificant change in host resistance to T. spiralis. Total serum IgG l evels, however, were increased in high-dose methadone-treated animals. Apparently, prolonged administration of morphine to rats resulted in immune suppression, mediating a slight, though biologically relevant, exacerbation of the T. spiralis infection, whereas methadone did not. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserve d.