Development pattern of the GABA_A-benzodiazepine receptor ionophore complex in primary cultures of cortical neurons

The development pattern of the GABA_A/benzodiazepine (BZ) receptor ionophore complex was characterized in mammalian cortical cultured neurons utilizing radioligand binding and GABA-induced ³⁶Cl-influx. The specific binding of [³H]flunitrazepam, [³H]Ro15-1788 and [³H]Ro15-4513 increased with time from day 3 to day 21. The EC₅₀ value and E_max of the GABA, muscimol and pentobarbital to enhance [³H]-flunitrazepam binding did not change during the development. Furthermore, GABA-induced ³⁶Cl^- influx also did not change during development from day 3 to day 21. However, the potency of ligands that bind to type-1 BZ receptors (alprazolam, zolpidem and C1218,872) to inhibit [³H]flunitrazepam binding increased from day 7 to day 21. Taken together, these data suggest the presence of type-II BZ receptors in early stages of the development which appears to change to type-I BZ receptors with age in the cortical neurons in culture.