The ontogeny of GABA receptors and glutamic acid decarboxylase in regions of the rat brain. Effect of prenatal exposure to diazepam.

The postnatal development of the binding of [3H]muscimol to both high-affinity and low-affinity GABA receptors and of the activity of glutamic acid decarboxylase has been studied in the frontal cortex, cerebellum, striatum and hypothalamus of the rat, after prenatal exposure to diazepam. The dams were injected subcutaneously with single daily doses of 1 mg diazepam/kg from day 7-20 of gestation. The developmental profiles of the binding of [3H]muscimol to high-affinity GABA receptors were very similar in both control and diazepam-treated offspring. Prenatal administration of drug revealed no significant alteration in the binding of [3H]muscimol. The results in controls supported the concept of a sequential development of this population of GABA receptors in relation to the different maturation of structures in the brain. For the study of low-affinity GABA receptors, the dams were treated in the same way and, additionally, 1 mg diazepam/kg/day was injected subcutaneously in the offspring from postnatal day 5-10. At postnatal days 21 and 90, no qualitative or quantitative differences in the binding of [3H]muscimol to low-affinity GABA receptors in control and diazepam-exposed groups of animals were observed. The developmental profiles of the activity of glutamic acid decarboxylase were qualitatively very similar in the four areas of the brain studied. Prenatal exposure to diazepam revealed a transient elevation of the activity of the enzyme up to 33% in the frontal cortex, the cerebellum and the hypothalamus in the first postnatal week. The possible functional significance of these alterations is discussed.