title: Idazoxan activates rat forebrain glycogen phosphorylase in vivo: a histochemical study.
abstract: In vitro experiments show norepinephrine activates glycogen phosphorylase and glycogenolysis in forebrain glia. The present study used idazoxan (5 mg/kg) to elevate NE in vivo and examined patterns of active (aGP) and total (tGP) glycogen phosphorylase reactivity in selected neocortical, hippocampal, diencephalic, and striatal sites using a histochemical method. In somatosensory neocortex, aGP reactivity was highest in Layer 4 with consistent reactivity in the barrel fields in vehicle-treated brains. In the hippocampus, the stratum lacunosum moleculare was highly reactive, while cell layers were least reactive. The dentate gyrus and CA3 were more reactive for aGP than CA1. In the diencephalon, the medial habenula was most reactive followed by the reticular nucleus of the thalamus. In the striatum, globus pallidus was most reactive. Reactivity patterns for tGP were similar to those for aGP, but more intense. The neocortex had the highest overall reactivity for tGP. An estimate of the percentage of aGP relative to tGP suggested the regions sampled had similar levels of median basal activation (approximately 65%). Idazoxan increased aGP reactivity in all regions of the neocortex assessed (layers 3-6 of primary and secondary somatosensory cortex and the barrel fields). The neuropil layers, but not the cell layers, of hippocampus were more reactive following idazoxan treatment. Idazoxan also increased aGP reactivity in the laterodorsal, paraventricular, and reticular nuclei of the thalamus. The largest idazoxan-induced changes, as an estimated percentage of tGP, occurred in the hippocampus (approximately 16% for stratum lacunosum moleculare and for CA1 stratum oriens). Increases ranged from approximately 3 to 6% in neocortex and were less than 3% in the diencephalic and striatal areas. These effects of idazoxan are consistent with a role for norepinephrine in activating forebrain glycogenolyis in vivo and supporting increased brain metabolism. They contrast with earlier evidence showing that idazoxan reduces 2-deoxyglucose uptake in these brain areas. Idazoxan, and norepinephrine, may preferentially recruit glycolytic over oxidative metabolism in the rat forebrain.
authors.affiliation: Psychology Department, Memorial University of Newfoundland, St. John's, Canada NL A1B 3X9.
authors.forename: Maria
authors.initials: M
authors.lastname: Fara-On
authors.forename: John H
authors.initials: JH
authors.lastname: Evans
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Harley
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000187:drug effects / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology*; D006651:Histocytochemistry; D019329:Idazoxan / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D016548:Prosencephalon / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000317:Adrenergic alpha-Antagonists; D006003:Glycogen; D003847:Deoxyglucose; D024981:Glycogen Phosphorylase; D009638:Norepinephrine; D019329:Idazoxan