Chloramphenicol decreases brain glucose utilization and modifies the sleep-wake cycle architecture in rats.
We studied the effects of chloramphenicol on brain glucose utilization and sleep-wake cycles in rat. After slightly anaesthetized animals were injected with [18F]fluoro-2-deoxy-D-glucose, we acquired time-concentration curves from three radiosensitive beta microprobes inserted into the right and left frontal cortices and the cerebellum, and applied a three-compartment model to calculate the cerebral metabolic rates for glucose. The sleep-wake cycle architecture was analysed in anaesthetic-free rats by recording electroencephalographic and electromyographic signals. Although chloramphenicol is a well-established inhibitor of oxidative phosphorylation, no compensatory increase in glucose utilization was detected in frontal cortex. Instead, chloramphenicol induced a significant 23% decrease in the regional cerebral metabolic rate for glucose. Such a metabolic response indicates a potential mismatch between energy supply and neuronal activity induced by chloramphenicol administration. Regarding sleep-wake states, chloramphenicol treatment was followed by a 64% increase in waking, a 20% decrease in slow-wave sleep, and a marked 59% loss in paradoxical sleep. Spectral analysis of the electroencephalogram indicates that chloramphenicol induces long-lasting modifications of delta-band power during slow-wave sleep.
Moulin-Sallanon
Marcelle
M
IFR19, Institut Fédératif des Neurosciences de Lyon, Bron, France. Marcelle.MoulinSallanon@hcuge.ch
Millet
Philippe
P
Rousset
Colette
C
Zimmer
Luc
L
Debilly
Gabriel
G
Petit
Jean-Marie
JM
Cespuglio
Raymond
R
Magistretti
Pierre
P
Ibáñez
Vicente
V
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002701:Chloramphenicol / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
D011500:Protein Synthesis Inhibitors; D002701:Chloramphenicol; D005947:Glucose