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Benzodiazepines and the developing rat: a critical review.

J C Tucker

    Neuroscience and Biobehavioral Reviews
    |January 1, 1985
    PubMed
    Summary

    Prenatal benzodiazepine exposure may cause developmental issues and lasting behavioral changes in rats, though high doses are needed to impact physical development. Research on GABA system interactions and seizure sensitivity remains debated.

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    Area of Science:

    • Neuroscience
    • Developmental Toxicology
    • Pharmacology

    Background:

    • Benzodiazepines are widely used drugs with known effects on the central nervous system.
    • Concerns exist regarding the safety of benzodiazepine exposure during critical developmental periods.
    • The GABA system is a primary target for benzodiazepines, playing a crucial role in neuronal inhibition.

    Purpose of the Study:

    • To review the effects of benzodiazepine exposure on neurochemical and physical development in immature animals, focusing on rats.
    • To examine evidence for lasting behavioral and physiological consequences following developmental benzodiazepine exposure.
    • To synthesize current knowledge on benzodiazepine actions within the developing GABA system and their impact on seizure activity.

    Main Methods:

    • Comprehensive literature review of studies on benzodiazepine effects in immature rats.
    • Analysis of data concerning neurochemical development, physical growth, and behavioral outcomes.
    • Evaluation of research on the interaction between benzodiazepines, GABA, and seizure thresholds during development.

    Main Results:

    • Neurochemical development data are generally consistent, but age-related variations in GABA enhancement of benzodiazepine binding are controversial.
    • Physical development is affected only by very high benzodiazepine doses.
    • Prenatal or neonatal exposure to specific benzodiazepines (e.g., diazepam, lorazepam, CGS 8216) can lead to lasting effects on startle responses, learning, behavior, and seizure susceptibility.

    Conclusions:

    • Developmental benzodiazepine exposure can induce persistent behavioral alterations in rats, though confounding variables complicate interpretation.
    • The impact on physical development requires high doses, but neurobehavioral effects are observed at lower exposure levels.
    • Further research is needed to clarify controversial findings regarding GABA system interactions and seizure sensitivity during development.

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