Neuropeptide YY1 receptors mediate morphine-induced reductions of natural killer cell activity

Morphine suppresses a number of immune parameters, such as natural killer (NK) cell activity and lymphocyte proliferation, by acting through mu-opioid receptors in the central nervous system. Prior studies have implicated the sympathetic nervous system in mediating the immunomodulatory effects of acute morphine treatment. However, the peripheral mechanism whereby morphine inhibits NK cell activity is not fully understood. The aim of the present study was to investigate the role of the sympathetic transmitter neuropeptide Y (NPY) in mediating morphine-induced immune alterations. The results showed that administration of the selective NPY Y, receptor antagonist BIBP3226 blocked morphine's effect on splenic, NK activity but did not attenuate the suppression splenocyte proliferative responses to ConA or LPS. Furthermore, intravenous NPY administration produced a dose-dependent inhibition of splenic NK activity but did not suppress lymphocyte proliferation. Recent studies from our laboratory have demonstrated that morphine modulates NK activity through a central mechanism that requires the activation of dopamine D, receptors in the nucleus accumbens. Results from the present study showed that microinjection of the D-1 receptor agonist SKF-38393 into the nucleus accumbens shell induced a suppression of NK activity that was reversed by BIBP3226. Collectively, these findings demonstrate that NPY Y-1 receptors mediate morphine's suppressive effect on NK activity and further suggest that opioid-induced increases in nucleus accumbens D-1 receptor activation inhibit splenic NK activity via NPY released from the sympathetic nervous system. (c) 2006 Elsevier B.V. All rights reserved.