GABA and benzodiazepine receptors in the offspring of dams receiving diazepam: Ontogenetic studies

Ontogenesis of the regulation of 3H-GABA and 3H-diazepam binding to rat brain plasma membranes treated with 0.05% Triton X-100 has been studied. The density of 3H-diazepam and 3H-GABA binding in cortex, cerebellum and corpus striatum at birth was approximately one third of the adult values. They increased at the same rate and reached the adult values between 14–21 days after birth. Study of the binding characteristics showed that the K D for high and low affinity for 3H-GABA, and for 3H-diazepam did not change during ontogenesis and the increase reflects only an increase of Bmax. The number of Triton X-100 treatments of crude synaptic membrane (CSM) required to maximize 3H-GABA for the high affinity component were different at various postnatal days: only one treatment was required in 1-day old rats, two in 7- and 14-day old rats and three in adult animals. In addition, the capability of muscimol to stimulate 3H-diazepam binding in both frozen-thawed and Triton X-100 treated membrane preparations decreased with increasing age. Binding of 3H-GABA and 3H-diazepam to brain of newborn rats whose dams received diazepam throughout pregnancy (100 mg/kg, × os, bid) was also studied. No significant differences were observed in the ontogenetic development of both bindings. However, in the cortex of these newborn rats the capability of muscimol to stimulate 3H-diazepam binding was greatly reduced in Triton X-100-treated membranes.