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 behavioral and physiological responses to cellular glucopenia. Antagonism of mu and kappa opioid receptors attenuates glucoprivic hyperphagia, findings that implicate 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 sites. Male rats were pretreated with beta-funaltrexamine (mu antagonist), Mr-1452 MS (kappa antagonist), or vehicle prior to intraperitoneal injection of the glucose antimetabolite, 2-deoxy-D-glucose (2DG), then sacrificed by transcardial perfusion 2 h later. Nuclear immunolabeling for the transcription factor, Fos, was observed in several preoptic and hypothalamic sites following 2DG administration. Rats pretreated with the mu antagonist exhibited significantly fewer Fos-positive neurons in the medial preoptic area and dorsomedial hypothalamic nucleus in response to 2DG, compared to vehicle-pretreated controls. Blockade of kappa receptors diminished 2DG and induced Fos staining in the paraventricular and supraoptic nuclei. Numbers of Fos-positive 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 the Fos stimulus-transcription pathway by local neurons in discrete hypothalamic sites.
Briski
K P
KP
Division of Basic Pharmaceutical Sciences, College of Pharmacy, Northeast Louisiana University, Monroe 71209-0470, USA. pybriski@alpha.nlu.edu
Teodecki
L
L
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology; D001575:Benzomorphans / Q000008:administration & dosage / Q000494:pharmacology; D003847:Deoxyglucose / Q000008:administration & dosage / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
D000963:Antimetabolites; D001575:Benzomorphans; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C029552:Mr 1452; C024524:beta-funaltrexamine; D003847:Deoxyglucose; D005947:Glucose