COCAINE BINDING-SITES IN FETAL-RAT BRAIN - IMPLICATIONS FOR PRENATAL COCAINE ACTION

Binding of [H-3]cocaine to membrane preparations from whole fetal rat brain was studied. High-affinity binding (10 nM cocaine) was detected as early as gestational day (GD) 15 and steadily increased across subs equent development. Saturation studies comparing [H-3]cocaine binding at GD20 and adulthood yielded similar K-D values, and LIGAND analyses favored a two-site model if an extended range of [H-3]cocaine concentr ations was used. Various monoamine uptake inhibitors displaced labeled cocaine with potencies consistent with the idea that [H-3]cocaine lab els the dopamine (DA), serotonin (5-HT), and possibly also the norepin ephrine (NE) transporters in whole fetal brain preparations. Synaptoso mal DA uptake was well developed by GD20, as was the potency of cocain e to inhibit such uptake. The results indicate that functional, monoam ine transporter related cocaine binding sites are present in the fetal rat brain. Such sites are likely to play an important role in mediati ng the direct interactions of prenatally-administered cocaine with dev eloping monoaminergic systems in both animals and humans.