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Consequences of chronic phenobarbital treatment on local cerebral glucose utilization in the developing rat
A Pereira de Vasconcelos1, S Boyet, A Nehlig
1I.N.S.E.R.M. U272, Université de Nancy I, France.
Insights
Chronic phenobarbital (PhB) exposure in rats reduces brain glucose metabolism and growth. These effects persist into adulthood, impacting numerous brain regions and confirming long-term behavioral deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Phenobarbital (PhB) is a widely used sedative and anticonvulsant.
- Early life exposure to certain drugs can have lasting effects on brain development.
- Understanding the long-term impact of PhB on the developing brain is crucial.
Purpose of the Study:
- To investigate the chronic effects of phenobarbital (PhB) on postnatal brain glucose metabolism in rats.
- To assess the long-term consequences of early PhB exposure on cerebral energy metabolism in adult rats.
Main Methods:
- Rats received daily subcutaneous injections of PhB (50 mg/kg) or saline from postnatal days 2-35.
- Local cerebral metabolic rates for glucose (LCMRglc) were measured in 58 brain structures at multiple postnatal stages (10, 14, 17, 21, 35 days) and adulthood.
- Body and brain weights were monitored throughout the study.
Main Results:
- PhB treatment significantly reduced LCMRglc in most brain regions until day 35, with some recovery by day 17.
- Long-term reductions in LCMRglc were observed in adult rats across 36 out of 58 brain regions studied.
- PhB exposure led to reduced body and brain weights and suggested a delay in auditory function acquisition.
Conclusions:
- Chronic early-life phenobarbital exposure causes significant, long-lasting deficits in cerebral glucose metabolism in rats.
- These metabolic changes in the adult brain correlate with previously observed behavioral deficits.
- The findings highlight the potential for developmental neurotoxicity of phenobarbital.
Abstract:
The influence of a chronic phenobarbital (PhB) treatment on postnatal evolution of local cerebral metabolic rates for glucose (LCMRglc) was studied in 58 cerebral structures of freely moving rats. The animals received a daily subcutaneous injection of PhB at a dose of 50 mg/kg between days 2 and 35 or an equivalent volume of saline for controls and were studied at 5 postnatal stages, i.e. 10, 14, 17, 21 and 35 days, and at the adult stage. Body and brain weights were both reduced by 6-21% over the whole period studied. PhB exposure induced significant decreases in LCMRglc during the period of pharmacological treatment, i.e. until 35 days, except at the stage of 17 days as well as long-term reductions in LCMRglc of adult rats in 36 out of the 58 brain regions studied. These decreases affected all systems studied, sensory systems as well as limbic, hypothalamic, motor and white matter areas. In addition to a growth retardation, PhB also seemed to be able to induce a delay in the acquisition of auditory function which matures early during postnatal life. The long-term deficits in cerebral energy metabolism due to PhB in the adult rat also confirm the behavioral deficits which have been shown previously after early PhB exposure.