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Phenobarbital during pregnancy alters operant behavior of offspring in C57BL/6J mice
Insights
Prenatal exposure to phenobarbital in C57BL/6J mice offspring resulted in reduced operant responding on fixed ratio schedules. These behavioral changes occurred even at doses not causing mortality or physical abnormalities.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Developmental Toxicology
Background:
- Phenobarbital is a widely used sedative-hypnotic and anticonvulsant medication.
- Prenatal exposure to various substances can lead to long-term neurobehavioral deficits in offspring.
- Previous studies have indicated potential adverse effects of phenobarbital on developing nervous systems.
Purpose of the Study:
- To investigate the long-term behavioral effects of prenatal phenobarbital exposure in mice.
- To determine if phenobarbital exposure during gestation causes lasting changes in operant responding.
- To assess dose-dependent effects and identify doses that induce behavioral abnormalities without significant mortality.
Main Methods:
- C57BL/6J mice were administered daily doses of phenobarbital (20, 40, or 80 mg/kg) during the last third of gestation.
- Offspring were assessed for operant behavior on fixed ratio schedules of reinforcement.
- Behavioral responses were compared between exposed offspring and control groups.
Main Results:
- Offspring exposed prenatally to phenobarbital exhibited a significant decrement in response rates compared to controls.
- The response decrement was more pronounced with increasing schedule demands (higher ratio requirements).
- The highest dose (80 mg/kg) was less effective in producing the behavioral decrement, potentially due to higher neonatal mortality at this dose.
Conclusions:
- Prenatal phenobarbital exposure induces long-lasting behavioral abnormalities in mice offspring.
- These deficits in operant responding occur at doses that do not cause significant neonatal mortality or morphological changes.
- The findings highlight the potential for subtle, yet significant, neurodevelopmental impacts of phenobarbital exposure.
Abstract:
Offspring of C57BL/6J injected daily with phenobarbital for the last third of pregnancy responded less than control animals when maintained on various fixed ratio schedules of reinforcement. The response decrement became more pronounced as the schedule demands were increased and was noted in offspring of both sexes. The higest dose (80 mg/kg) was less effective than the 2 lower doses (20 mg and 40 mg/kg) in producing the decrement which may reflect a selection factor due to high neonatal mortality previously reported at this dose. The study provides no evidence of the mechanism mediating the long term behavioral abnormality but does clearly extend the finding of such changes to doses which do not produce increased neonatal mortality or noticeable morphological changes.