Effects of Central Administration of Morphine on Immune Status in Lewis and Wistar Rats

Abstract

It has been well established that systemic administration of morphine is immunomodulatory and that this effect is mediated by opioid receptors (1, 2, 3). Prior research in our laboratory has shown that a single systemic administration of morphine induces naltrexone-reversible, dose-dependent alterations in lymphocyte proliferation to T- and B-cell mitogens, interleukin-2 and γ-interferon production, and natural killer cell cytotoxicity (1). To induce these effects, morphine could be acting peripherally on opioid receptors found on circulating lymphocytes or could be acting at opioid receptors in the central nervous system. There is increasing evidence for the role of the central nervous system in morphine’s immune modulation. Peripheral administration of N-methylmorphine, a form of morphine which does not cross the blood-brain barrier, does not result in changes in immune status (4). Moreover, a significant naltrexone-reversible suppression of natural killer cell (NK) activity results from intracranial administration of the drug into the lateral ventricle (4). These findings indicate that morphine acts at opioid receptors within the central nervous system to induce changes in the immune system. Furthermore, a single microinjection of morphine into the periaqueductal gray (PAG) of the brain results in naltrexone-reversible suppression of natural killer cell activity suggesting that this may be the site of action for morphine’s immunomodulatory effects (5).