Synchronous postnatal increase in α1 and γ2L GABAA receptor mRNAs and high affinity zolpidem binding across three regions of rat brain

The objective of this study was to correlate postnatal changes in levels of mRNAs encoding predominant GABAA receptor subunits with a functional index of receptor development. This study is the first to quantify the temporal relationship between postnatal changes in predominant GABAA receptor mRNAs and zolpidem-sensitive GABAA receptor subtypes. In Experiment 1, we measured zolpidem displacement of 3H-flunitrazepam from rat cerebral cortex, hippocampus, and cerebellum at 0, 6, 14, 21, 29, and 90 postnatal days. Three independent 3H-flunitrazepam sites with high (Ki=2.7±0.6 nM), low (Ki=67±4.8 nM), and very low (Ki=4.1±0.9 mM) affinities for zolpidem varied in regional and developmental expression. In Experiment 2, we used RNAse protection assays to quantify levels of α1, α2, β1, β2, γ2S and γ2L mRNAs in the above regions at the same postnatal ages. Although there was a high degree of regional variation in the developmental expression of zolpidem-sensitive GABAA receptors and subunit mRNAs, a dramatic increase in high affinity zolpidem binding sites and α1 mRNA levels occurred within all three regions during the second postnatal week. Furthermore, a temporal overlap was observed between the rise in α1 mRNA and high affinity zolpidem binding and a more prolonged increase in γ2L in each region. These results point to the inclusion of the α1 and γ2L subunits in a GABAA receptor subtype with a high zolpidem affinity and suggest that a global signal may influence the emergence of this subtype in early postnatal life.