Expression of Fos-Like Proteins in the Preoptic Area and Hypothalamus of the Rat Brain Following Intracerebral or Peripheral Administration of Colchicine

Abstract

Colchicine is frequently employed as a pharmacologic tool to enhance perikaryal neuropeptide concentrations, in order to facilitate mapping of functional neuron populations in the brain. However, it is not clear if effects of Colchicine on central neurons include transcriptional activation. The following studies utilized immunocytochemical techniques to evaluate the effects of intracer-ebroventricular (icv) drug treatment on Fos-like immunoreactivity (Fos-li) in preoptic and hypo-thalamic neurons. Since colchicine is administered orally in the treatment of gout-associated arthritis, additional experiments examined whether intragastric delivery of colchicine elicits pro-tooncogene expression by neurons in the brain. Groups of adult male rats were treated with colchicine by icv injection (150 μg/3.0 μl 0.9% saline) or by gavage (4.0 mg/1.0 ml 0.9% saline); vehicle-treated controls received saline alone. All animals were sacrificed 24 hr after drug or vehicle treatment. Serial 25 μm brain sections were processed for Fos-like immunoreactivity using anti-human Fos_4–17 antibodies (Ab-2, Oncogene Sciences) in conjunction with avidin-biotin immuno-peroxidase cytochemistry. These studies revealed negligible immunolabeling for Fos 24 hr after vehicle treatment. 24 hr after intracerebral delivery of colchicine, Fos-li was observed within the medial preoptic area, the arcuate nucleus, the supraoptic nucleus, and parvocellular neurons in the paraventricular nucleus. Animals treated with colchicine by gavage exhibited Fos-immunopositive neurons in the same sites, but additional immunolabeling for Fos was also observed within the median preoptic nucleus, suprachiasmatic nucleus, dorsomedial nucleus, and magnocellular neurons in the paraventricular nucleus. These results suggest, first of all, that neuronal responses to colchicine exposure include the synthesis of Fos-like proteins in a number of brain sites, at least over the time frame examined here. The present findings that protooncogene expression occurs within central neurons in response to intragastric drug administration suggest that neuronal activation may in response to drug-induced neural afferent and/or endocrine stimuli of peripheral origin.