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 [14C]2-deoxyglucose procedure, in 73 brain regions at 10, 30, 90 and 180 min after administration of oCRF 10 µg and at 90 min after oCRF 0.1, 1 and 100 µg. oCRF 10 µg 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 µg) 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 µg) 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.