Involvement of central mu- but not delta- or kappa-opioid receptors in immunomodulation

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.