Prenatal exposure to benzodiazepine--I. Prenatal exposure to lorazepam in mice alters open-field activity and GABAA receptor function.
Prenatal exposure to benzodiazepines may lead to developmental abnormalities in humans and animals. To assess the behavioral and neurochemical effects of such exposure, pregnant mice were treated with lorazepam, 2 mg/kg/day, from days 13-20 of gestation, and open-field activity was assessed in offspring at 3 and 6 weeks of age and the function of GABAA receptors at 6 weeks of age. Activity was increased in mice exposed to lorazepam, compared to untreated or vehicle-treated controls at 3 weeks, but was unchanged at 6 weeks. Muscimol-stimulated uptake of chloride was decreased in lorazepam-treated mice, compared to controls, with a decrease in maximum uptake but no change in the EC50 for muscimol. Concentrations of lorazepam in maternal plasma and brain showed a similar brain:plasma ratio as previously reported and concentrations in fetal brain were about 50% of maternal levels. Lorazepam persisted for 48 hours after birth in dams but not in the offspring. These results indicate persistent behavioral and neurochemical alterations after prenatal exposure to lorazepam. This model may be useful in assessing other effects of prenatal exposure to benzodiazepine.
Chesley
S
S
Department of Psychiatry, Tufts University School of Medicine, Boston, MA.
Lumpkin
M
M
Schatzki
A
A
Galpern
W R
WR
Greenblatt
D J
DJ
Shader
R I
RI
Miller
L G
LG
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D008140:Lorazepam / Q000493:pharmacokinetics / Q000494:pharmacology*; D008431:Maternal-Fetal Exchange; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D011247:Pregnancy; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values
D002712:Chlorides; D011963:Receptors, GABA-A; D009118:Muscimol; D008140:Lorazepam