ASSESSMENT OF THE INVOLVEMENT OF CENTRAL-NERVOUS-SYSTEM AND PERIPHERAL OPIOID RECEPTORS IN THE IMMUNOMODULATORY EFFECTS OF ACUTE MORPHINE TREATMENT IN RATS
K. Fecho et al., ASSESSMENT OF THE INVOLVEMENT OF CENTRAL-NERVOUS-SYSTEM AND PERIPHERAL OPIOID RECEPTORS IN THE IMMUNOMODULATORY EFFECTS OF ACUTE MORPHINE TREATMENT IN RATS, The Journal of pharmacology and experimental therapeutics, 276(2), 1996, pp. 626-636
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.