THE FOS PROTOONCOGENE PROTEIN - REGULATION BY MORPHINE IN THE RAT HYPOTHALAMUS

Mechanisms by which opiates alter neuronal functions, including neuroendocrine functions, are not well defined. We have previously demonstrated that morphine rapidly and transiently increases expression of the proto-oncogene c-fos in the rat caudateputamen. This regulation of the c-fos gene by morphine may represent a portion of the intracellular cascade coupling activation of opiate receptors on the cell surface to subsequent alterations in neuropeptide gene expression. In the present study, we have focussed on effects of morphine on c-fos expression in the ventromedial hypothalamus, which contains estrogen-concentrating neurons and a large number of neurons expressing the opioid proenkephalin and Proopiomelanocortin. The hypothalamus has been identified as a "final common pathway" between the remainder of the central nervous system and the pituitary gland. As a marker for c-fos expression, we have detected pp50 c-fos (FOS) protein immunocytochemically, using a polyclonal antibody to the M peptide of FOS, and revealed an intense nuclear stain in many neurons. Labeled nuclei were drawn by camera lucida from 12 matched sections (one side only) covering the rostral and middle levels of the ventromedial nucleus of six rats given morphine and six given phosphate buffered saline. Morphine treatment significantly increased the number and density of immuno-labeled nuclei in the ventromedial nucleus, but not in the arcuate nucleus. These results suggest effects of morphine (directly or indirectly) on neurons in the ventromedial hypothalamic nucleus, despite the relative absence of morphine receptors in this nucleus. These results may also provide an anatomical basis for neuroendocrine alterations following morphine treatment. © 1990.