title: Prenatal benzodiazepine administration. II. Lorazepam exposure is associated with decreases in [35S]TBPS binding but not benzodiazepine binding.
abstract: 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.
authors.affiliation: Department of Pharmacology, New England Medical Center, Boston, MA 02111.
authors.forename: L G
authors.initials: LG
authors.lastname: Miller
authors.forename: S
authors.initials: S
authors.lastname: Chesley
authors.forename: W R
authors.initials: WR
authors.lastname: Galpern
authors.forename: D J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: R I
authors.initials: RI
authors.lastname: Shader
mesh_terms: 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
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011963:Receptors, GABA-A; C041598:t-butylbicyclophosphorothionate receptor; C037476:tert-butylbicyclophosphorothionate; D008140:Lorazepam