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Influence of early neonatal phenobarbital exposure on cerebral energy metabolism and behavior
A Pereira de Vasconcelos1, C Colin, D Desor
1INSERM U272, Université de Nancy, France.
Insights
Early phenobarbital exposure in rats reduced brain glucose use and impaired learning and memory. These effects persisted into adulthood, suggesting long-term impacts of neonatal barbiturate treatment on brain development and function.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pharmacology
Background:
- Neonatal exposure to certain medications can have lasting effects on brain development.
- Phenobarbital is a commonly used barbiturate with potential neurodevelopmental impacts.
- Understanding the long-term consequences of early phenobarbital exposure is crucial for pediatric care.
Purpose of the Study:
- To investigate the effects of early chronic phenobarbital exposure on local cerebral glucose utilization (LCGU) in rats.
- To assess the short- and long-term behavioral consequences of neonatal phenobarbital treatment.
- To explore the relationship between LCGU, brain metabolism, and learning abilities following early phenobarbital exposure.
Main Methods:
- Rats were treated daily with phenobarbital (50 mg/kg) or saline from postnatal day 2 to 35.
- Local cerebral glucose utilization (LCGU) was measured at different time points (10-35 days and 70-90 days).
- Behavioral tests included open field, spontaneous alternation, non-rewarded T-maze, and rewarded eight-arm maze.
Main Results:
- Phenobarbital exposure led to sustained reductions in LCGU in hippocampal and cerebellar areas.
- The maturation pattern of LCGU rates was altered by phenobarbital treatment.
- Treated rats showed decreased exploratory behavior, impaired spontaneous alternation, and slower learning in a non-rewarded T-maze.
- No significant changes in performance were observed in a rewarded eight-arm maze.
Conclusions:
- Early phenobarbital exposure causes significant, long-lasting alterations in brain glucose metabolism and behavior in rats.
- Neonatal barbiturate exposure impairs specific learning and memory functions, particularly those associated with the hippocampus.
- There is no direct correlation found between hippocampal energy metabolism rates and impaired learning in adult rats after early phenobarbital exposure.
Abstract:
The influence of an early chronic phenobarbital (PhB) exposure on local cerebral glucose utilization (LCGU) and on behavior was studied in the rat. The animals were treated from Postnatal Day 2 to Postnatal Day 35 by a daily injection of 50 mg/kg PhB or by saline and tested between 10 and 35 days for short-term effects of the drug on LCGU and between 70 and 90 days for long-term effects of PhB on LCGU and behavior. PhB induced short- and long-lasting reductions in the overall rates of LCGU in hippocampal and cerebellar areas, but no significant changes in LCGU in the different cell layers of these two cerebral areas. PhB also changed the pattern of maturation of the rates of LCGU as compared to control subjects. The barbiturate treatment induced a decrease in the exploratory behavior of PhB- as compared to saline-treated rats in the open field, as well as a significant 25% decrease in the rate of spontaneous alternation with delay. In addition, PhB-treated rats needed significantly more time than control animals to perform their trials in the nonrewarded T maze testing. However, the neonatal barbiturate exposure did not induce changes in performances of adult rats in the rewarded eight arm maze. The results of the present study show that there is no apparent correlation between the rates of energy metabolism in the hippocampus and the impairment of learning abilities of adult rats in behavioral tests related to the hippocampus.