Transport of 14C-gamma-aminobutyric acid into brain, cerebrospinal fluid and choroid plexus in neonatal and adult rats

Abstract

In general blood to brain entry of amino acids is greater in the neonatal rats compared to the adults. gamma-Aminobutyric acid (GABA), a neurotransmitter amino acid, shows limited transport across the blood-brain barrier (BBB) in the adult rat. Characteristics of GABA entry into the immature rat brain is yet to be addressed. This investigation was set to study the entry of GABA into brain of the neonatal rat compared to the adult. Using the bilateral in situ brain perfusion technique, the entry of 14C-GABA into brain, cerebrospinal fluid (CSF) and lateral ventricles choroid plexuses was studied in the adult and neonatal rats. 14C-GABA uptake into neonatal rat brain after 20 min perfusion was 0.116+/-0.014 ml g(-1), approximately twice that of the adults (P<0.01). Half saturation constant, K(m), did not change with age (P>0.05), whereas maximal transport into the brain, V(max), was reduced from 0.152 to 0.068 nmol min(-1) g(-1) showing a significant reduction with age (P<0.05). In the neonate the entry of GABA into the CSF was dominant when compared to that into the brain, this could be due to a greater diffusional component, K(d), which was detected to be high in the neonate. In conclusion, the uptake of 14C-GABA into brain of the immature rats exceeded that in the adults which is thought to be due to both greater maximal transport and greater diffusion in the neonate compared to the adult.