ASSESSMENT OF THE INVOLVEMENT OF CENTRAL-NERVOUS-SYSTEM AND PERIPHERAL OPIOID RECEPTORS IN THE IMMUNOMODULATORY EFFECTS OF ACUTE MORPHINE TREATMENT IN RATS

The present study assessed the involvement of opioid receptors both in the central nervous system (CNS) and in the periphery (i.e., on immun ocytes) in the immune alterations produced by acute morphine treatment in rats. The first experiment showed that the in vitro suppressive ef fects of morphine on the mitogen-stimulated proliferation of splenic a nd blood lymphocytes are produced only by a Very high concentration of morphine and are not naltrexone-reversible. These results suggest tha t the in vitro immunomodulatory effects of morphine are not mediated b y classical opioid receptors on immunocytes. A second experiment showe d that s.c. doses of N-methylnaltrexone that do nor gain access to the CNS, as determined by the tail-withdrawal assay, do not antagonize th e suppressive effects of a single, s.c. injection of morphine on the m itogen-stimulated proliferation of splenic and blood lymphocytes, sple nic natural killer cell activity and the production of interferon-gamm a by stimulated splenocytes. Only a high s.c. dose of N-methylnaltrexo ne that does gain access to the CNS, as determined by the tail-withdra wal assay, blocks morphine's immunomodulatory effects. A third experim ent demonstrated that N-methylnaltrexone is 4 to 5 log units more pote nt in antagonizing most of the immune alterations produced by a single , s.c. injection of morphine when administered i.c.v. than s.c. Taken together, the results of the present study strongly suggest that CNS o pioid receptors play an important role in the immune alterations produ ced by acute morphine treatment in rats.