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, [H-3]muscimol and [H-3]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 [H-3]muscimol binding (P < 0.001) and 45% (P < 0.001) in [H-3]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.