title: Hippocampal gamma-aminobutyric acid and benzodiazepine receptors after early phenobarbital exposure.
abstract: Mice were exposed to phenobarbital (PhB) prenatally (PreB offspring) by feeding their mothers 3 g/kg PhB in milled food on gestation days 9-18, or neonatally by directly injecting pups of intact mothers with daily dose of 50 mg PhB on postnatal days 2-21 (NeoB offspring). At age 22 or 50 days, the offspring were tested for gamma-aminobutyric acid (GABA) up take in the hippocampus and in the rest of the brain. In addition, [3H]muscimol and [3H]flunitrazepam binding in the hippocampus and cortex were measured in the offspring at age 22 and 50 days. Long-term decrease in GABA uptake was found in the NeoB group. A 23% decrease was found in 22-day-old mice (P < 0.001) and a 22% decrease in 50-day-old mice (P < 0.05). In addition, there was a 22% decrease in GABA uptake in the brain of 22-day-old PreB mice (P < 0.05). An increase of 52% in [3H]muscimol binding (P < 0.001) and 45% (P < 0.001) in [3H]flunitrazepam binding were measured in the hippocampus in the 22-day-old NeoB mice; no differences were found in affinity. The differences were short-term and could no longer be detected at age 50 days. No differences were found in the cortex; unlike NeoB, PreB mice did not differ from controls. The results suggest upregulation of the GABAergic system in early PhB exposed mice.
authors.affiliation: Melvin A. and Eleanor Ross Laboratory for Studies in Neural Birth Defects, Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: C G
authors.initials: CG
authors.lastname: Pick
authors.forename: A
authors.initials: A
authors.lastname: Weizman
authors.forename: F
authors.initials: F
authors.lastname: Fares
authors.forename: M
authors.initials: M
authors.lastname: Gavish
authors.forename: B I
authors.initials: BI
authors.lastname: Kanner
authors.forename: J
authors.initials: J
authors.lastname: Yanai
mesh_terms: D000818:Animals; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018079:Receptors, GABA / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D018079:Receptors, GABA; D011963:Receptors, GABA-A; D010634:Phenobarbital