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Persistent alterations in GABAA receptor binding and function after prenatal lorazepam administration in the chick
L G Miller1, R B Roy, C L Weill
1Department of Medicine, LSU Medical Center, New Orleans.
Brain Research Bulletin
|September 1, 1989
Summary
Prenatal exposure to lorazepam, a benzodiazepine, caused lasting changes in the GABAergic system in chickens. These neurochemical alterations may affect behavior and development.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Benzodiazepines are known to cause behavioral abnormalities in animals exposed prenatally.
- The GABAergic system is the primary target of benzodiazepine action.
Purpose of the Study:
- To investigate neurochemical alterations in the GABAergic system following prenatal benzodiazepine exposure.
- To utilize a chick model to isolate the effects of prenatal exposure from maternal influences.
Main Methods:
- Adult chickens exposed to lorazepam in ovo (10 days) were studied.
- GABAergic system neurochemistry was assessed, including receptor binding and function.
- Specific binding assays using [35S]TBPS were performed.
Main Results:
- Prenatal lorazepam exposure altered the GABAA receptor complex in adult chickens.
- Decreased binding occurred at the chloride channel site ([35S]TBPS).
- Reduced coupling between the chloride channel and GABA binding sites, and diminished GABAA receptor function in chloride uptake were observed.
Conclusions:
- Persistent neurochemical alterations in the GABAergic system result from prenatal benzodiazepine exposure.
- These alterations may underlie subsequent behavioral and developmental changes.