Conditioned immunomodulation: investigations of the role of endogenous activity at μ, κ, and δ opioid receptor subtypes

Abstract

The present investigations were designed to determine the role of activity at μ, κ, and δ opioid receptor subtypes in conditioned immunomodulation by evaluating the effects of selective opioid receptor antagonists on conditioned stimulus-induced alterations in immune status. Lewis rats were exposed to an aversive conditioned stimulus that was developed through pairings with electric footshock. This aversive conditioned stimulus induces a reduction in splenic natural killer cell activity, splenocyte proliferation in response to mitogens, and diminished levels of interferon- γ (IFN- γ) production by splenocytes. Intracerebroventricular (ICV) administration of the opioid antagonist naltrexone or the μ 1-selective antagonist naloxonazine blocked conditioned alterations of immune status, indicating that activity at μ-opioid receptors is involved in conditioned immunomodulation. Further support for the involvement of μ-opioid receptors within the central nervous system is provided by data showing that peripheral administration of naloxonazine, at doses shown to be effective when administered ICV, had no effect on conditioned alterations of immune status. Ventricular administration of the κ receptor antagonist nor-binaltorphimine (nor-BNI) did not antagonize the immunomodulatory effects of the conditioned stimulus. Administration of the δ receptor antagonist naltrindole also did not antagonize the conditioned alterations of immune status. Collectively, the results of this study indicate that the alterations of immune status produced by an aversive conditioned stimulus require activity at μ-opioid receptors, possibly μ 1, within the central nervous system.