Hippocampal gamma-aminobutyric acid and benzodiazepine receptors after early phenobarbital exposure.
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.
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Melvin A. and Eleanor Ross Laboratory for Studies in Neural Birth Defects, Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Weizman
A
A
Fares
F
F
Gavish
M
M
Kanner
B I
BI
Yanai
J
J
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*
D018079:Receptors, GABA; D011963:Receptors, GABA-A; D010634:Phenobarbital