Effects of mu and kappa opioid receptor antagonists on glucoprivic induction of Fos immunoreactivity in the rat preoptic area and hypothalamus

Interoreceptors in the central nervous system elicit compensatory behaviora l and physiological responses to cellular glucopenia. Antagonism of mu and kappa opioid receptors attenuates glucoprivic hyperphagia, findings that im plicate these peptidergic receptors in the central processing of metabolic regulatory signals. Several hypothalamic structures of critical importance for the regulation of energy balance exhibit one or both of these receptors . The following studies investigated the role of these opioid receptors in glucoprivic induction of immediate-early gene expression in these brain sit es. Male rats were pretreated with beta-funaltrexamine (mu antagonist), Mr- 1452 MS (kappa antagonist), or vehicle prior to intraperitoneal injection o f the glucose antimetabolite, 2-deoxy-D-glucose (2DG), then sacrificed by t ranscardial perfusion 2 h later. Nuclear immunolabeling for the transcripti on factor, Fos, was observed in several preoptic and hypothalamic sites fol lowing 2DG administration. Rats pretreated with the mu antagonist exhibited significantly fewer Fos-positive neurons in the medial preoptic area and d orsomedial hypothalamic nucleus in response to 2DG, compared to vehicle-pre treated controls. Blockade of kappa receptors diminished 2DG and induced Fo s staining in the paraventricular and supraoptic nuclei, Numbers of Fos-pos itive cells in the arcuate nucleus and ventrolateral hypothalamic area were not altered by either antagonist. The present data implicate mu and kappa opioid receptors in neural mechanisms underlying glucoprivic induction of t he Fos stimulus-transcription pathway by local neurons in discrete hypothal amic sites. (C) 1999 Elsevier Science Inc.