Postnatal development of GABA binding sites and their endogenous inhibitors in rat brain

Developmental changes in the affinity and density of binding sites for the inhibitory neurotransmitter, GABA, were studied in well-washed, frozen-thawed or Triton detergent extracted forebrain and cerebellar membranes from rats of 1 day, 10 days and 12 weeks postnatal age. Two populations of binding sites with similar affinities to those found in adult brain membrane preparations were found in the corresponding preparations from 1- and 10-day-old animals. While there appeared to be little developmental change in binding affinities, the density of GABA binding sites increased markedly with increasing age. At each age, freeze-thawing or Triton extraction caused successive increases in the affinity of GABA binding found in washed synaptosomal membranes. This indicates the presence of endogenous inhibitors of GABA binding in rat forebrain and cerebellum before most synapses have formed. Furthermore, there appeared to be greater endogenous inhibition of GABA binding in neonatal rat brain than in the adult, suggesting that decreases in endogenous inhibitor levels during maturation may be related to the development of synaptic activity.