Studies completed in both humans and animals have shown that opioids have s
ignificant effects on the immune system via pharmacological interactions wi
th the opioid receptor. However, the type of opioid receptor at which morph
ine binding produces changes in immune status has not been well characteriz
ed. To determine the type of opioid receptor involved in opioid-induced imm
une alterations, the present study assessed the effects of agonists selecti
ve for the mu-, delta-, and kappa-opioid receptors. The site of action (i.e
.. peripheral vs central) at which opioids produce immune changes was inves
tigated by injecting the agonists directly into the left lateral ventricle
of the brain. Specifically. Lewis rats received an intracerebroventricular
administration of (D-Ala(2),N-Me-Phe(4),Gly-ol(5)]enkephalin (DAMGO), a mu-
receptor selective agonist, [D-Pen(2,5)]enkephalin (DPDPE), a delta-opioid
receptor agonist, or U69,593, a kappa-receptor agonist. Immune assessments
completed 1 h following drug administration showed that the mu-receptor sel
ective agonist DAMGO produced a dose-dependent decrease in natural killer c
ell activity and T-lymphocyte proliferation to the mitogen concanavalin A (
Con A); no immunological changes were found following DPDPE or U69,593 trea
tment. Calculation of the number of white blood cells per sample showed no
differences between rats treated with saline and rats treated with any of t
he selective agonists. Administration of the opioid antagonist N-methylnalt
rexone prior to DAMGO treatment attenuated the DAMGO-induced changes in imm
une status. Results from the present study indicate that the immunomodulato
ry effects of opioids can be attributed to interactions with the mu-opioid
receptor. (C) 2000 Academic Press.