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 effects of IL-1 are the result of both direct action on immune cells and indirect action on a regulatory cascade mediated through the hypothalamus. Chronic exposure to substances of abuse, such as morphine, appears to modulate immunoresponsiveness by mechanisms not yet defined. The expression of FOS, the protein product of the c-fos proto-oncogene, has been widely used as an anatomical marker for monitoring neuronal activity. 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 demonstrate that chronic exposure to morphine attenuates the cellular responsiveness to IL-1 and to morphine in the PVN and SON, whereas pretreatment with naloxone, an opiate receptor antagonist, does not reverse the effect of IL-1 on FOS expression. The results not only confirm that the PVN and SON are neuroanatomical sites where the actions of both morphine and IL-1 converge, but also indicate that chronic exposure to morphine may desensitize the cellular response involved in hypothalamic functions through an IL-1-dependent pathway.
Chang
S L
SL
Department of Biology, Seton Hall University, South Orange, NJ 07079, USA. changsul@lanmail.shu.edu
Patel
N A
NA
Romero
A A
AA
Thompson
J
J
Zadina
J E
JE
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D004343:Drug Implants; D016762:Genes, fos; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000378:metabolism
D004343:Drug Implants; D007375:Interleukin-1; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D009270:Naloxone; D009020:Morphine