Time- and dose-dependent effects of corticotropin releasing factor on cerebral glucose metabolism in rats.
The time course and the relation to dose of locomotor activity and of the regional cerebral metabolic rates for glucose (rCMRglc) were measured in freely moving Sprague-Dawley rats after intracerebroventricular administration of ovine corticotropin releasing factor (oCRF). Motor activity was determined using a familiar photocage cell. rCMRglc was measured, using the quantitative autoradiographic [(14)C]2-deoxyglucose procedure, in 73 brain regions at 10, 30, 90 and 180 min after administration of oCRF 10 microg and at 90 min after oCRF 0.1, 1 and 100 microg. oCRF 10 microg increased motor activity in a sustained fashion and increased rCMRglc with different time courses throughout brain regions. In cerebellar regions rCMRglc increases peaked at 90 min and were sustained up to 180 min. In non-cerebellar regions rCMRglc increases peaked at 90 min but declined thereafter. At lower doses (0.1 and 1 microg) oCRF increased rCMRglc in fewer brain regions (1 and 5 regions affected, average increases 1% and 7%) including cerebellar areas and brainstem sensory nuclei and decreased rCMRglc in medial prefrontal cortex. At the highest dose (100 microg) oCRF induced large and widespread rCMRglc increases in cerebellar, brainstem, hypothalamic, limbic and neocortical areas (40 brain regions affected, average increase 32%). The findings indicate that cerebellar areas and brainstem nuclei are highly sensitive to oCRF and may mediate oCRF autonomic and behavioral effects.
Freo
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Department of Neurosciences, University of Padova, Italy. ulderico.freo@libero.it
Ori
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C
Weiss
S R B
SR
Perini
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D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002250:Carbon Radioisotopes; D003346:Corticotropin-Releasing Hormone; D003847:Deoxyglucose; D005947:Glucose