Neurotransmitter changes during development of cortical neuronal cultures.

Benzodiazepine (BDZ) ligands clonazepam (CLO) and Ro5-4864 which preferentially bind to neuronal and non-neuronal elements, respectively, have been used to follow neuronal and non-neuronal development in fetal murine cortical cultures. CLO-displaceable BDZ binding, choline acetyltransferase (CAT) activity, high-affinity delta-aminobutyric acid (GABA) uptake, and glutamic acid decarboxylase (GAD) activity reached a maximum value at the end of the second week in culture reflecting maximum neuronal maturation and development. There is a developmental order of these four functions: CAT activity (main enzyme in the synthesis of acetylcholine, a stimulating neurotransmitter) reached maximal levels first, 3H-GABA uptake and CLO-displaceable flunitrazepam receptor binding reached maximal levels 1 day later, and 4 days later GAD activity (primary enzyme in the synthesis of GABA, an inhibitor neurotransmitter) reached maximal levels.