Lorazepam administration during embryonic development alters GABAA receptor binding and function.
Prenatal exposure to diazepam has been reported to lead to behavioral alterations in young and mature animals, but the neurochemical basis of this effect is uncertain. To examine effects of embryonic benzodiazepine exposure on the gamma-aminobutyric acidergic (GABA)ergic) system, we assessed binding and function at the GABAA receptor complex in chick embryos treated with lorazepam, 2 mg/kg, for 2-10 days. There was no change in benzodiazepine receptor binding in cortex after lorazepam administration, but a decrease in the number of chloride channel sites was observed. Overall function at the GABAA receptor complex as assessed by chloride uptake into cortical synaptoneurosomes was decreased after 10 days of lorazepam, and possibly increased after 4 days of lorazepam. Similar results were obtained when embryos were treated for 2- and 4-day periods beginning on day 8. These results indicate that chronic lorazepam administration to embryos alters binding and function in the GABA system measured soon before hatching. These alterations, if persistent, may contribute to the behavioral changes seen in animals exposed prenatally.
Miller
L G
LG
Department of Medicine, LSU Medical Center, New Orleans 70112.
Weill
C L
CL
Roy
R B
RB
Gaver
A
A
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002642:Chick Embryo; D002712:Chlorides / Q000493:pharmacokinetics; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005445:Flunitrazepam / Q000378:metabolism; D008140:Lorazepam / Q000008:administration & dosage*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate; D008140:Lorazepam