Fentanyl-induced Seizures Activate Subcortical Brain Metabolism

Abstract

Neurophysiologic studies show epileptoid activity during high-dose narcotic anesthesia. The 14C-2-deoxyglucose method was used to study the local cerebal glucose metabolism (1-CMRg) during high-dose fentanyl-induced epileptoid discharges as seen by EEG in ventilated rats. Fentanyl was administered i.v. at 2 dose levels (200 .mu.g/kg, n = 5 and 400 .mu.g/kg, n = 8). Seven unanesthetized animals served as controls. During fentanyl administration, the EEG was characterized by the appearance of isolated high voltage (> 100 .mu.V) spike and polyspike and wave complexes at a frequency of 1 every 1 to 4 s, superimposed on a baseline of reduced frequency and voltage. Isolated ictal discharges (spike or sharp waves at a frequency of 12 to 20/s) rarely were superimposed on the spike and polyspike activity. Fentanyl administration induced a significant (P < 0.05) decrease of the 1-CMRg in the majority of the 37 brain structures surveyed. A clear relationship between 1-CMRg and epileptoid activity appeared when the anatomic areas were grouped into functional systems. Cerebral metabolism was globally decreased in the visual and sensorimotor systems (53-78%), in the white matter structures (76-78%) and reticular formation (59-69%) with both fentanyl treatments. The largest deviation from this trend appeared in the limbic system. Here, with both treatments, the 1-CMRg in the claustrum, septal nucleus, amygdala and ventral areas of CA1 and CA3 of the hippocampus remained at control values. At the higher fentanyl dosage, there was a more widespread depression of 1-CMRg in the rest of the brain while in the limbic system this effect was reversed, with the 1-CMRg returning to control values in the hippocampus (CA1), dentate gyrus and interpeduncular nucleus. The relative hypermetabolism in limbic system structures during fentanyl-induced epileptoid activity, coupled with a significant reduction of glucose utilization in the rest of the brain, suggests a role for the limbic system in the genesis of seizure activity during fentanyl administration.