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

Abstract

We studied the effects of chloramphenicol on brain glucose utilization and sleep-wake cycles in rat. After slightly anaesthetized animals were injected with [18 F]fluoro-2-deoxy-D-glucose, we acquired time-concentration curves from three radiosensitive b microprobes inserted into the right and left frontal cortices and the cerebellum, and applied a threecompartment 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 slowwave sleep.

Astrocytic Modulation of Sleep Homeostasis and Cognitive Consequences of Sleep Loss

“…Thus, we added Dox back to the diet for 2–3 weeks to inhibit transgene expression (Fig 1 O–S) and asked whether dnSNARE animals can revert to a wildtype phenotype. This is a difficult control to perform since antibiotics have been reported to affect some sleep parameters such as SWA (Moulin-Sallanon et al, 2005). Therefore, we closely examined the effect of Dox on wildtype animals, and determined that it had no significant effect on three sleep parameters which we used as markers for reversibility in the dnSNARE animals.…”

MicroPET Outperforms Beta-Microprobes in Determining Neuroreceptor Availability under Pharmacological Restriction for Cold Mass Occupancy

“…A major theoretical advantage of beta-microprobes includes their high temporal resolution to capture the peak of the time-activity curve. However, during time-activity curve pre-processing and in accordance with literature (Pain et al, 2002 ; Zimmer et al, 2002 ; Ginovart et al, 2004 ; Moulin-Sallanon et al, 2005 ; Märk et al, 2013 ; Balasse et al, 2014 ), we were forced to resample the curves to larger time frames due to high signal noise associated with beta-microprobe recordings. We resampled the data to μPET frames: 2 × 10 s, 3 × 20 s, 3 × 30 s, 3 × 60 s, 3 × 150 s, 9 × 300 s. In this way, the beneficial theoretical temporal resolution of 1 s was lost.…”

“…Following a stereotaxic implantation in the rat brain, radiosensitive beta-microprobes can measure the local concentration of a radiolabeled molecule within a few millimeters around its tip. This technique proved useful for different purposes; such as cerebral blood flow measurements (Weber et al, 2003 ), metabolic studies (Moulin-Sallanon et al, 2005 ), radiotracer evaluation (Wyss et al, 2007 ), arterial input function measurements (Warnock et al, 2011 ), and drug challenge experiments (Ginovart et al, 2004 ). μPET offers a non-invasive alternative, by visualizing radiotracer distribution in the entire brain and enabling longitudinal studies through intra-animal comparisons.…”

Scientific Opinion on Chloramphenicol in food and feed

“…with 400 mg/kg b.w. of chloramphenicol succinate or chloramphenicol (chemical form not specified) (Moulin-Sallanon-et al, 2005;Chahboune et al, 2008). Chloramphenicol caused a significantly increased waking time (approximately 65 %) a moderately decrease in slow-wave sleep and a marked loss (60 %) in paradoxical sleep compared with control rats.…”