Chloramphenicol decreases brain glucose utilization and modifies the sleep–wake cycle architecture in rats

AbstractWe 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 β 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.