EXPRESSION OF FOS-LIKE PROTEINS IN THE PREOPTIC AREA AND HYPOTHALAMUSOF THE RAT-BRAIN FOLLOWING INTRACEREBRAL OR PERIPHERAL ADMINISTRATIONOF COLCHICINE

Colchicine is frequently employed as a pharmacologic tool to enhance p erikaryal neuropeptide concentrations, in order to facilitate mapping of functional neuron populations in the brain. However, it is not clea r if effects of colchicine on central neurons include transcriptional activation. The following studies utilized immunocytochemical techniqu es to evaluate the effects of intracerebroventricular (icv) drug treat ment on Fos-like immunoreactivity (Fos-li) in preoptic and hypothalami c neurons. Since colchicine is administered orally in the treatment of gout-associated arthritis, additional experiments examined whether in tragastric delivery of colchicine elicits protooncogene expression by neurons in the brain. Groups of adult male rats were treated with colc hicine by icv injection (150 mu g/3.0 mu l 0.9% saline) or by gavage ( 4.0 mg/l.0 ml 0.9% saline); vehicle-treated controls received saline a lone. All animals were sacrificed 24 hr after drug or vehicle treatmen t. Serial 25 mu m brain sections were processed for Fos-like immunorea ctivity using antihuman Fos(4-17) antibodies (Ab-2, Oncogene Sciences) in conjunction with avidin-biotin immunoperoxidase cytochemistry. The se studies revealed negligible immunolabeling for Fos 24 hr after vehi cle treatment. 24 hr after intracerebral delivery of colchicine, Fos-l i was observed within the medial preoptic area, the arcuate nucleus, t he supraoptic nucleus, and parvocellular neurons in the paraventricula r nucleus. Animals treated with colchicine by gavage exhibited Fos-imm unopositive neurons in the same sites, but additional immunolabeling f or Fos was also observed within the median preoptic nucleus, suprachia smatic nucleus, dorsomedial nucleus, and magnocellular neurons in the paraventricular nucleus. These results suggest, first of all, that neu ronal responses to colchicine exposure include the synthesis of Fos-li ke proteins in a number of brain sites, at least over the time frame e xamined here. The present findings that protooncogene expression occur s within central neurons in response to intragastric drug administrati on suggest that neuronal activation may in response to drug-induced ne ural afferent and/or endocrine stimuli of peripheral origin.