title: Chronic treatment with morphine and ethanol, but not cocaine, attenuates IL-1 beta activation of FOS expression in the rat hypothalamic paraventricular nucleus.
abstract: Interleukin-1 beta (IL-1 beta) is a key mediator of immunological and pathological responses to stress, injury and disease and it has been suggested to have profound effects on neuroendocrine-immune functions. We have shown that central treatment with IL-I beta induces the expression of FOS proto-oncogene protein immunoreactivity (FOS-IR) in several hypothalamic nuclei including the paraventricular nucleus (PVN). Since FOS expression has been used as an anatomical marker of neuronal function, these results suggested that the involvement of IL-1 beta in the neuro-endocrine-immune axis may be mediated through the PVN. Treatment with several substances of abuse has been shown to modify immune function in vivo and in vitro. In this study, we compared the effects of morphine, ethanol and cocaine on IL-1 beta induction of FOS-IR in the rat hypothalamus. Acute treatment with morphine or ethanol induced FOS-IR in several nuclei including the PVN. Cocaine, which induced FOS-IR in the Caudate-Putamen (CPU), nucleus Accumbens (nAcc) and Locus Coeruleus (LC), however, did not induce FOS-IR in the PVN. Chronic treatment with morphine desensitized FOS responsiveness to morphine and IL-1 beta in the PVN since FOS-IR was no longer induced by IL-1 beta or morphine in the PVN after this treatment. Similarly, chronic ethanol treatment desensitized FOS responsiveness to ethanol and to IL-1 beta in the PVN. By contrast, chronic cocaine did not affect FOS responsiveness to IL-1 beta in the PVN even though the treatment was able to desensitize the FOS responsiveness to acute cocaine in the CPU, nAcc, and LC. These results suggest that the PVN may be a site where actions of IL-1 beta converge with those of morphine and ethanol, but not cocaine, to modulate neuro-endocrine-immune functions.
authors.affiliation: Department of Biology, Seton Hall University, South Orange, New Jersey 07079, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Chang
authors.forename: V
authors.initials: V
authors.lastname: Kenigs
authors.forename: R L
authors.initials: RL
authors.lastname: Moldow
authors.forename: J E
authors.initials: JE
authors.lastname: Zadina
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007375:Interleukin-1; D000431:Ethanol; D009020:Morphine; D003042:Cocaine