FOS EXPRESSION INDUCED BY INTERLEUKIN-1 OR ACUTE MORPHINE TREATMENT IN THE RAT HYPOTHALAMUS IS ATTENUATED BY CHRONIC EXPOSURE TO MORPHINE

Interleukin-1 (IL-1) is a cytokine involved in a variety of biological activities. It has been hypothesized that the immunomodulatory effect s of IL-1 are the result of both direct action on immune cells and ind irect action on a regulatory cascade mediated through the hypothalamus . Chronic exposure to substances of abuse, such as morphine, appears t o modulate immunoresponsiveness by mechanisms not yet defined. The exp ression of FOS, the protein product of the c-fos proto-oncogene, has b een widely used as an anatomical marker for monitoring neuronal activi ty. We have previously shown that acute treatment with either morphine or IL-1 induces FOS immunoreactivity in the rat brain, including the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. In this study, using immunocytochemical staining of FOS, we demonstra te that chronic exposure to morphine attenuates the cellular responsiv eness to IL-1 and to morphine in the PVN and SON, whereas pretreatment with naloxone, an opiate receptor antagonist, does not reverse the ef fect of IL-1 on FOS expression. The results not only confirm that the PVN and SON are neuroanatomical sites where the actions of both morphi ne and IL-1 converge, but also indicate that chronic exposure to morph ine may desensitize the cellular response involved in hypothalamic fun ctions through an IL-1-dependent pathway.