GABA-stimulated chloride uptake and enhancement by diazepam in synaptoneurosomes from rat brain during prenatal and...

The present study was undertaken to evaluate the ability of diazepam (DZ) to elicit a response in the brains of developing animals. gamma-Aminobutyric acid (GABA)-stimulated 36Cl- uptake in the presence and absence of DZ was measured in synaptoneurosomal preparations from whole brain of fetal rats at 20 and 21 days gestation and from cerebral cortex of rats at 7, 14, 21, 28 and 60-90 days postnatal age. The ability of GABA to stimulate 36Cl- uptake in a concentration-dependent manner was evident from gestational day 20. The EC50 for GABA stimulation but not the maximum stimulation increased significantly from day 20 to day 21 of gestation. Postnatally, only moderate changes in the EC50 were evident, but the maximum 36Cl- transported increased significantly from 7 to 14 days and remained stable thereafter. DZ enhanced GABA-mediated 36Cl- influx from 20 days gestation, and this enhancement was seen as a decrease in the EC50 for GABA stimulation. However, DZ also significantly increased maximum GABA-stimulated 36Cl- transport in synaptoneurosomal preparations at 21 days gestation and at 7 days postnatal age, a response to DZ not seen at older ages. DZ had a less robust effect on GABA-mediated 36Cl- transport at 28 days postnatal age than at any other age, a result consistent with functional observations of decreased responsivity to DZ in late juvenile, early adolescent rats. The benzodiazepine antagonist Ro 15-1788 prevented the effect of DA on GABA-stimulated 36Cl- uptake in tissue from 21-day fetuses and from 60- to 90-day-old adults.(ABSTRACT TRUNCATED AT 250 WORDS)