Prenatal benzodiazepine administration. II. Lorazepam exposure is associated with decreases in [35S]TBPS binding but not benzodiazepine binding.
Prenatal benzodiazepine exposure has been associated with neurobehavioral alterations in humans and animals. To determine effects of prenatal benzodiazepine exposure on binding at the benzodiazepine and t-butylbicyclophosphorothionate (TBPS) sites on the GABAA receptor in mature offspring, we treated mice with lorazepam, 2 mg/kg/day, during days 13-20 of gestation. Binding was assessed at 6 weeks of age. There were no differences among controls, vehicle- or lorazepam-exposed mice in benzodiazepine receptor binding determined in vivo or in vitro. However, receptor density for [35S]TBPS binding sites was decreased in lorazepam-exposed offspring compared to the other groups. These data are consistent with prior neurochemical results indicating decreased TBPS binding and GABAA receptor function in several systems.
Miller
L G
LG
Department of Pharmacology, New England Medical Center, Boston, MA 02111.
Chesley
S
S
Galpern
W R
WR
Greenblatt
D J
DJ
Shader
R I
RI
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005260:Female; D008140:Lorazepam / Q000633:toxicity*; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011963:Receptors, GABA-A; C041598:t-butylbicyclophosphorothionate receptor; C037476:tert-butylbicyclophosphorothionate; D008140:Lorazepam