Persistent alterations in GABAA receptor binding and function after prenatal lorazepam administration in the chick.
Behavioral abnormalities have been reported in young and adult animals exposed to benzodiazepines prenatally. The presence of neurochemical alterations in the GABAergic system after prenatal benzodiazepine exposure was assessed in a chick model which avoids prenatal and postnatal maternal effects. The GABAA receptor complex, the presumed site of benzodiazepine action, was altered in adult chickens previously exposed to lorazepam for 10 days in ovo. Binding was decreased at the putative chloride channel site labeled by [35S]TBPS, coupling was decreased between this site and the GABA binding site, and function of the GABAA receptor in chloride uptake was diminished in animals exposed to prenatal lorazepam. Persistent neurochemical alterations in the GABAergic system accompany prenatal benzodiazepine exposure, and may influence subsequent behavior and development.
Miller
L G
LG
Department of Medicine, LSU Medical Center, New Orleans.
Roy
R B
RB
Weill
C L
CL
Lopez
F
F
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002642:Chick Embryo; D002645:Chickens; D002712:Chlorides / Q000378:metabolism; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D008140:Lorazepam / Q000008:administration & dosage / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate; D008140:Lorazepam