Stoichiometry of muscimol and benzodiazepine binding sites in developing mouse cerebellum

The ontogeny of high affinity GABAA and central benzodiazepine receptors in the mouse cerebellum was investigated by measuring [3H]muscimol and [3H]flunitrazepam binding to membrane preparations during postnatal development. In the P2 fraction, [3H]muscimol binding was much more abundant than [3H]flunitrazepam binding at all ages. [3H]muscimol Bmax exhibited a peak around postnatal day 25 while [3H]flunitrazepam binding did not follow a parallel course. These results can be explained by the preferential presence in cerebellum of certain variants of the different subunits of the GABAA receptor complex and with different topographical distributions of the different receptor subtypes. Development dependent changes of organelle distribution during subcellular fractionation also contributed to the described developmental pattern.